ABSTRACTThe millennial generation of human beings is at risk of the epidemic of lifestyle disorders such as obesity, diabetes and cardiac vascular diseases. With the advancement in science and technology, today’s society has an excess of food supply and machines to lessen their physical burden, resulting in energy imbalance. Obesity and in association with chronic inflammation and dyslipidemia impairs the functioning of the cells, markedly by inducing endoplasmic reticulum (ER) stress, thereby hampering cellular responses of the anabolic hormone insulin. However, the associated underlying mechanisms that regulate the aforesaid disorder are less understood.
PHLPP1 is a hydrophobic motif targeted phosphatase that inactivates Akt, the master regulator of insulin-mediated glucose homeostasis. Our knowledge about the role of PHLPP1 in regulating glucose metabolism is very limited warranting deeper studies with mechanistic insights. In the current study, we show that PHLPP1 expression was augmented in the insulin-responsive tissues like skeletal muscle, liver, and adipose of insulin-resistant rodents which also displayed ER stress, a key cellular driver of insulin resistance. As 70% of glucose uptake is mediated by the skeletal muscle, we further examined the effect of PHLPP1 on skeletal muscle insulin resistance (IR).
- Thesis Statement
- Structure and Outline
- Voice and Grammar
- Conclusion
Using chemical and molecular biology tools in both cell-based and in vivo studies, we identified that PHLPP1 promotes the development of ER stress in skeletal muscle. Importantly, ablation of PHLPP1 improved glucose clearance from systemic circulation along with heightened expression of skeletal muscle insulin responsive glucose transporter, GLUT-4. Upon further investigation, we observed that the endogenous interaction of PHLPP1, but not PP2Ac or PP2C?, with AMPK, was enhanced under ER stress. Furthermore, we show that PHLPP1 directly dephosphorylates AMPK at Thr172 in myoblasts without influencing its upstream kinase, LKB1. Importantly, the association between endogenous PHLPP1 and AMPK was enriched in soleus muscle of high-fat diet fed mice, while a minimal change was detected in the basal association of PP2Ac and AMPK highlighting the pathophysiological in vivo relevance of PHLPP1. Moreover, through biochemical studies, we demonstrate that PHLPP1? is phosphorylated by ERK1/2 at Ser932 under ER stress response which enhanced its ability to interact with and dephosphorylate its substrates (AMPK/Akt). We here show that ERK1/2 mediated phosphorylation of PHLPP1 inactivated AMPK to facilitate ER stress and inhibit GLUT4 expression resulting in insulin resistance (IR).
Collectively, our data position PHLPP1 as a key regulator of ER stress-mediated IR, regulating not only insulin-stimulated Akt signaling but also AMPK mediated insulin independent pathway.GRAPHICAL ABSTRACT:PHLPP1 promotes ER stress-mediated IR in skeletal muscle. ER stress augments the expression as well as ERK1/2 mediated activating phosphorylation of PHLPP1 which by inactivation of AMPK facilitates ER stress and restrict glucose uptake both in response to insulin and independent of insulin by direct dephosphorylation of Akt and AMPK respectively. In addition, PHLPP1 also limits the expression of GLUT4 expression upon induction of ER stress. (Figure adapted from Behera et al.
2018 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 1)TABLE OF CONTENTS TOC o “1-4” h z u Chapter 1: Introduction and review of literature PAGEREF _Toc432143167 h 11.1Insulin and insulin secretions PAGEREF _Toc432143168 h 41.1.
1The Discovery of Insulin PAGEREF _Toc432143169 h 61.1.2Structure and Chemical Properties of Insulin PAGEREF _Toc432143170 h 201.1.3Biosynthesis PAGEREF _Toc432143171 h 27 1.
1.4 Biphasic Mode of insulin secretion…………………………………… 1.1.5 Factors influencing Insulin Secretion…………………………………. 1.2Insulin Signalling PAGEREF _Toc432143172 h 321.
2.1Insulin signalling through Akt PAGEREF _Toc432143173 h 341.3Negative regulators of insulin signalling PAGEREF _Toc432143178 h 801.3.1Phosphoprotein Phosphatases PAGEREF _Toc432143179 h 811.3.
2Lipid Phosphatases PAGEREF _Toc432143180 h 891.3.3Adaptor Proteins PAGEREF _Toc432143181 h 921.3.4Inhibitory Ser/Thr phosphorylation PAGEREF _Toc432143182 h 98 1.4 Insulin resistance and its drivers……………………………………….
. 1.4.
1Genetic causes PAGEREF _Toc432143183 h 991.4.2Environmental causes PAGEREF _Toc432143184 h 1071.4.3 Molecular causes 1.
4.3.a Lipotoxicity/dyslipidemia…………………………………………1.4.3.
b Inflammation……………………………………………………..1.4.3.c Hyperglycemia……………………………………………………1.4.
3.d Mitochondrial Dysfunction and ROS Formation………………..
1.4.3.b ER Stress……………………………………………………….. 1.5 Endoplasmic Reticulum Stress and Unfolded Protein response1.
5.1Adaptation Phase 1.5.1.a Recognition of unfolded proteins 1.5.
1.b Transduction of the unfolded protein signal1.5.2Alarm Phase1.5.
3Apoptotic Phase 1.5.3.a Intrinsic pathways 1.5.
3.b Extrinsic pathways 1.6 ER stress and Type 2 diabetes1.6.1ER stress-mediated insulin resistance in various tissues 1.
6.1.a Hypothalamus 1.6.1.
a Adipose tissue 1.6.1.
a Liver 1.6.1.a Pancreatic ? cells 1.6.1.a Skeletal muscle1.7PHLPP: Emerging target for therapeutics PAGEREF _Toc432143178 h 801.
7.1Domain composition and function PAGEREF _Toc432143179 h 811.7.2Substrates of PHLPP PAGEREF _Toc432143180 h 891.7.3Multifaceted Regulation of PHLPP PAGEREF _Toc432143181 h 921.7.
4PHLPP in physiology and pathology PAGEREF _Toc432143182 h 98Chapter 2: ER stress ; inflammation augments PHLPP1 PAGEREF _Toc432143185 h 1102.1.Modulation of PHLPP1 expression alters glucose metabolism PAGEREF _Toc432143186 h 1122.2.PHLPP1 expression is enhanced in animals displaying insulin resistance PAGEREF _Toc432143187 h 1192.3.
PHLPP1 expression is enhanced under inflammation in skeletal muscle PAGEREF _Toc432143188 h 1232.4.PHLPP1 expression is enhanced upon ER stress in skeletal muscle PAGEREF _Toc432143189 h 1272.5.Summary PAGEREF _Toc432143194 h 146Chapter 3: AMPK? a novel substrate of PHLPP1 PAGEREF _Toc432143195 h 1473.
1.PHLPP1 regulates the activity of AMPK? PAGEREF _Toc432143196 h 1503.2.PHLPP1 interacts with AMPK? PAGEREF _Toc432143197 h 1533.3.In vitro dephosphorylation of AMPK? by PHLPP1 PAGEREF _Toc432143200 h 1673.4.
PHLPP1 facilitates ER stress by inhibition of AMPK activity PAGEREF _Toc432143201 h 169 3.5. PHLPP1 suppresses GLUT4 expression PAGEREF _Toc432143202 h 174 3.6. Summary………………………………………………………………….
Chapter 4: PHLPP1 is phosphorylated by ERK1/2 upon ER stress PAGEREF _Toc432143203 h 1754.1.In silico analysis of PHLPP1 phosphorylation sites PAGEREF _Toc432143204 h 177 4.2. PHLPP1 is a substrate of ERK1/2……………………………………….
. PAGEREF _Toc432143205 h 1794.3.Confirmation of Ser932 as the site of ERK1/2 phosphorylation PAGEREF _Toc432143206 h 1834.4.PHLPP1 is phosphorylated by ERK1/2 in intact cells PAGEREF _Toc432143207 h 1874.5.ER stress induces ERK1/2 mediated PHLPP1 phosphorylation PAGEREF _Toc432143208 h 1924.
6.Summary PAGEREF _Toc432143209 h 196Chapter 5: Consequences of ERK1/2-mediated PHLPP phosphorylation PAGEREF _Toc432143203 h 1755.1.Impact of PHLPP1 phosphorylation on its cellular functions PAGEREF _Toc432143204 h 1775.1.
1Effect of p-PHLPP1 on induction of ER stress…………………… 5.1.2Effect of p-PHLPP1 on skeletal muscle insulin resistance………..5.2.Impact of PHLPP1 phosphorylation on catalytic activity PAGEREF _Toc432143205 h 1795.3.
Impact of PHLPP1 phosphorylation upon substrate interaction PAGEREF _Toc432143206 h 1835.4.Impact of PHLPP1 phosphorylation on its protein stability PAGEREF _Toc432143207 h 1875.5.Summary PAGEREF _Toc432143208 h 192Chapter 6: Discussion and Future Perspectives PAGEREF _Toc432143211 h 202Chapter 7: Materials and Methods PAGEREF _Toc432143212 h 222References PAGEREF _Toc432143213 h 234Appendix PAGEREF _Toc432143214 h 276ABBREVIATIONS2-NBDG 2-(N-7-nitrobenz-2-oxa-1,3-diazol-4-ylamino)-2-deoxyglucose)4E-BP1 4E-binding protein 14-PBA 4-phenyl butyric acidACC Acetyl-CoA carboxylaseADP Adenosine diphosphateAGEs Advanced glycation end productsAMP Adenosine monophosphateAMPK AMP-activated protein kinaseAICAR 5-aminoimidazole-4-carboxamide-1-b-D-ribofuranosideAP-1 Activator protein-1APAF1 Apoptotic protease activating factor 1ARE Antioxidant response elementAS160 Akt Substrate of 160 KDaASK1 Apoptosis signal-regulating kinase 1ATF Activating Transcription FactorATP Adenosine triphosphateAUC Area under the curveBak Bcl-2-like protein 7Bax Bcl-2-like protein 4Bcl-2 B-cell lymphoma 2?-TrCP BetaTransducin repeats-Containing ProteinsBim Bcl-2-like protein 11BiP Binding immunoglobulin proteinbZIP Basic Leucine ZippercAMP 3?,5?-cyclic adenosine monophosphateCBP CBP (CREB-binding protein)CCR C-C chemokine receptorCD Cluster of differentiationCDS Coding sequenceCHOP C/EBP Homologous ProteinCK1 Casein kinase 1CREB cAMP response element binding proteinCRP C-reactive proteinDAG DiacylglycerolDIO Diet induced obesityDEPTOR DEP domain-containing mTOR-interacting proteinDHet Double Heterozygous deficiency of insulin receptor and IRS-1 allelesDMEM Dulbecco’s modified Eagle’s mediumDNA Deoxyribonucleic acidDTT 1,4-dithiothreitolEDTA Ethylenediaminetetraacetic acidEGFR Epidermal growth factor receptoreIF Eukaryotic translation initiation factor ER Endoplasmic reticulumERAD ER-associated degradationERSE ER stress response elementsER stress Endoplasmic reticulum stressERK Extracellular signal-regulated kinaseFAS Fatty acid synthaseFBS Fetal bovine serumFFA Free fatty acidsFKBP51 FK506-binding protein of 51 kDaFGF Fibroblast growth factorFoxO Forkhead box OG6Pase glucose 6-phosphataseGADD Growth Arrest and DNA Damage-Inducible ProteinGIP glucose-dependent insulinotropic polypeptideGLP-1 glucagon-like peptide-1GLS1 Golgi localization sequences 1GLUT4 Glucose transporter type 4Grb Growth factor receptor-bound proteinGRP78 78 kDa glucose-regulated proteinGSIS glucose-stimulated insulin secretionGSK-3beta Glycogen synthase kinase-3betaGST Glutathione STransferaseHA HemagglutininHDAC Histone deacetylasesHFD High fat diethIAPP Human islet amyloid polypeptideHIF Hypoxia-inducible factorHSD High sucrose dietHSP Heat shock proteinIFN InterferonIGF1 Insulin-like growth factor 1IKK Ikappa B kinaseIL InterleukiniNOS Inducible nitric oxide synthaseIP7 inositol pyrophosphate (diphosphoinositol pentakisphosphate 5-PP-1(1,2,3,4,6)IP5).IR Insulin resistanceIRE1 Inositol Requiring Enzyme 1IRS insulin receptor substrateJAK Janus tyrosine kinaseJNK C-Jun N-terminal kinaseLAR Leukocyte common antigen-related protein tyrosine phosphataseLIF Leukemia inhibitory factorLKB1 Liver Kinase B1lncRNAs long noncoding RNAsLPS LipopolysaccharideMAPK Mitogen activated protein kinaseMBTPS2 Membrane-bound transcription factor protease site 2MCP-1 Monocyte chemoattractant protein-1MEFs Mouse embryo fibroblastsMEK1 MAPK/ERK kinase 1MIDY Mutant INS-gene-induced Diabetes of YouthmiR/miRNAs MicroRNAsmLST8 mammalian lethal with SEC13 protein 8Mst1 Mammalian sterile 20-like kinasemTORC1 mammalian target of rapamycin complex 1mTORC2 mammalian target of rapamycin complex 2NAD Nicotinamide adenine dinucleotideNADPH Nicotinamide adenine dinucleotide phosphate hydrogenNEFAs Nonesterified fatty acidsNF-Y Nuclear transcription factor YNFAT Nuclear factor of activated T cellsNF?B Nuclear factor ?BNLR NOD (nucleotide-binding oligomerization-domain protein)-like receptorNLRC NOD-LRR (leucine-rich repeat) family with CARD (caspase recruitment domain) NO Nitric oxideNrf2 Nuclear factor erythroid 2–related factor 2p300/Ep300 E1A-associated protein p300PAK1 p21- activated kinase 1PACAP pituitary adenylate cyclase-activating polypeptidePCR Polymerase chain reactionPDE3B Phosphodiesterase 3BPDK-1 3-phosphoinositide-dependent protein kinase 1PEPCK Phosphoenolpyruvate carboxykinasePERK Protein kinase-like endoplasmic reticulum kinasePGC-1? Peroxisome proliferator-activated receptor gamma coactivator 1-alphaPHLPP PH (pleckstrin homology) domain Leucine-rich repeat Protein PhosphatasePI3K Phosphatidylinositol 3 kinasePIMT PRIP interacting protein with methyl transferase domainPIP2 phosphorylates phosphatidylinositol 4,5-bisphosphatePIP3 phosphatidylinositol (3,4,5)-triphosphate PKA protein kinase APKC Protein kinase CpNPP p-nitrophenyl phosphatePPAR? Peroxisome Proliferator-activated Receptor ?PP1 Protein phosphatase 1PP2A Protein phosphatase 2APP2B Protein phosphatase 2BPP2C Protein phosphatase 2CPRAS40 40kDa Proline-rich Akt substratePSP Protein serine/threonine phosphatasePTEN Inositol 3-phosphatase and tensin homologue deleted on chromosome 10PTP Protein tyrosine phosphatasePTP1B protein-tyrosine phosphatase 1BRHEB Ras homolog enriched in brainRNA Ribonucleic acidROS Reactive oxygen speciesRP reserve poolsRRP readily releasable poolsRTKs Receptor tyrosine kinasesS6K p70 ribosomal protein S6 kinases SCD Stearoyl-CoA desaturaseSCOP Scn circadian oscillatory proteinSFB Streptavidin Flag BiotinSGT1 Suppressor of G2 allele of SKP1 homologSHIP (SH2)-containing inositol phosphataseSH2 Src-homology2shRNA Small hairpin RNAsiRNA Small interfering RNASKIP Skeletal muscle kidney-enriched inositol polyphosphate phosphataseSNP Single nucleotide polymorphismSOCS Suppressor of cytokine signalingSP1 Specificity protein-1SR Sarcoplasmic reticulumSREBP Sterol regulatory element binding proteinss RNA Single stranded RNASTAT Signal transducer and activator of transcriptionsTWEAK Soluble tumour necrosis factor-like weak inducer of apoptosisT2D Type 2 diabeticTBC1D4 TBC1 Domain Family Member 4TCPTP T-cell protein tyrosine phosphatase TGF-? Transforming growth factor-?TLR Toll-like receptorTRAF TNF receptor associated factorTrb3 Tribbles homolog 3Treg Regulatory T cellTSC Tuberous sclerosis proteinsTUDCA Taurine-conjugated ursodeoxycholic acidTXNIP Thioredoxin-interacting proteinUDP Uridine 5′-diphosphoUPR Unfolded protein responseUSP Ubiquitin specific proteaseUTR Untranslated regionVLDLs Very low-density lipoproteinsWFS Wolfram syndromeWT Wild typeXBP1 X-box-binding proteinLIST OF FIGURESFigure PageChapter 11.1 Factors influencing Insulin Secretion at the cellular level 51.2 Schematic representation of Insulin signalling 121.
3 Negative regulators of insulin signalling 141.4 Insulin resistance and its drivers 161.5 Schematic representation of Endoplasmic Reticulum Stress 191.7 Domain architecture of PHLPP isoforms. 211.7 Role of PHLPP in physiology and pathology.
24Chapter 22.1 PHLPP1 alters glucose sensing machinery in skeletal muscle 1132.2 PHLPP1 expression is elevated in insulin-resistant animals 1142.
3 TNF-? enhances the expression of PHLPP1 and ER stress markers 1162.4 PHLPP1 expression is enhanced by ER stress 1182.5 PHLPP1 promotes ER stress 120Chapter 33.1 PHLPP1 decreases AMPK? activity. 1523.2 Interaction of PHLPP1 with AMPK? is enhanced upon ER stress.
1543.3 AMPK is a novel target of PHLPP1. 1563.4 PHLPP1 facilitates ER stress by inhibiting AMPK. 1583.5 PHLPP1 suppresses GLUT4 expression. 160Chapter 44.
1 Schematic representation of PHLPP1? protein. 1784.2 PHLPP1 is phosphorylated by ERK1/2 1804.3 PHLPP1 is phosphorylated at Ser932 residue by ERK1/2 in vitro. 1824.4 PHLPP1 is a substrate of ERK1/2 in intact cells. 1844.
5 Phosphorylation of PHLPP1 at Ser932 is enhanced upon ER stress. 186Chapter 55.1 Ser932 PHLPP1? phosphorylation is required for ER stress induction and inhibition of insulin-stimulated glucose uptake. 1785.2 ERK1/2 mediated PHLPP1 phosphorylation augments its catalytic activity 1805.3 Ser932 phosphorylation of PHLPP1? promotes substrate interaction. 1825.
4 Enhanced expression of PHLPP1 is independent of phosphorylation at Ser932. 184LIST OF TABLESTable PageChapter 11.1 List of miRNAs regulating the expression of PHLPP 9Chapter 44.1 Predicted kinase sites of PHLPP1? (Scansite prediction) 1724.2 Conserved putative ERK1 phosphorylation site on PHLPP1? 1724.3 Predicted ERK D-domains of PHLPP1? (Scansite motif analysis) 1724.
4 ELISA results for phospho-specific antibody after the 3rd immunization 172Insulin and insulin signalling:The Discovery of Insulin:History of insulin discovery starts way back in 1921 when a Canadian physician Frederick Banting and medical student Charles H. Best isolated insulin from the pancreatic extracts of dogs and administered its chilled saline extracts intravenously in dogs to lower the blood glucose levels in dogs with pancreatectomy induced diabetes. Later, biochemist Collip in collaboration with Banting and Best demonstrated that the enriched and purified extract of insulin was responsible for the restoration of hepatic glycogen and peripheral clearance of ketones. In January 1922 the first human trial of insulin was performed on a 14-year-old diabetic boy and a noted improvement in clinical symptoms and biochemical abnormalities upon administration of pancreatic extract was observed. Subsequently, early in 1923, Eli Lilly started production of porcine insulin by enhancing purification through iso-electric precipitation and in the same year the Nobel Prize for the discovery of insulin was awarded to Banting and McLeod in 1923 ADDIN EN.CITE <EndNote><Cite><Author>Bliss</Author><Year>1993</Year><RecNum>192</RecNum><DisplayText>2</DisplayText><record><rec-number>192</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>192</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Bliss, M.
</author></authors></contributors><auth-address>Department of History, University of Toronto, Canada.</auth-address><titles><title>The history of insulin</title><secondary-title>Diabetes Care</secondary-title><alt-title>Diabetes care</alt-title></titles><periodical><full-title>Diabetes Care</full-title><abbr-1>Diabetes care</abbr-1></periodical><alt-periodical><full-title>Diabetes Care</full-title><abbr-1>Diabetes care</abbr-1></alt-periodical><pages>4-7</pages><volume>16 Suppl 3</volume><keywords><keyword>Adolescent</keyword><keyword>Diabetes Mellitus, Type 1/blood/*drug therapy</keyword><keyword>Drug Industry/history</keyword><keyword>History, 19th Century</keyword><keyword>History, 20th Century</keyword><keyword>Humans</keyword><keyword>Insulin/*history/*therapeutic use</keyword><keyword>Ontario</keyword></keywords><dates><year>1993</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0149-5992 (Print) 0149-5992 (Linking)</isbn><accession-num>8299476</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/8299476</url></related-urls></urls></record></Cite></EndNote>2.Structure and Chemical Properties of Insulin:Chemically insulin is a peptide whose amino acid sequence was identified in 1952. Insulin is composed of two peptide chains, chain A (21 amino acids) and chain B (30 amino acids) in most species.
Chains A and B are linked together by two disulphide bonds, which join the N- and C-terminal helices of the chain A to the central helix of chain B. In pro-insulin, a connecting peptide called C-peptide links the N-terminus of the Chain A to the C-terminus of the Chain B ADDIN EN.CITE <EndNote><Cite><Author>Dodson</Author><Year>1998</Year><RecNum>193</RecNum><DisplayText>3</DisplayText><record><rec-number>193</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>193</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Dodson, G.
</author><author>Steiner, D.</author></authors></contributors><auth-address>National Institute of Medical Research, London, UK. r-sumray@nimr.
mrc.ac.uk</auth-address><titles><title>The role of assembly in insulin's biosynthesis</title><secondary-title>Curr Opin Struct Biol</secondary-title><alt-title>Current opinion in structural biology</alt-title></titles><periodical><full-title>Curr Opin Struct Biol</full-title><abbr-1>Current opinion in structural biology</abbr-1></periodical><alt-periodical><full-title>Curr Opin Struct Biol</full-title><abbr-1>Current opinion in structural biology</abbr-1></alt-periodical><pages>189-94</pages><volume>8</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Biological Transport, Active</keyword><keyword>Cytoplasmic Granules/metabolism</keyword><keyword>Golgi Apparatus/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/*biosynthesis/*chemistry/genetics</keyword><keyword>Islets of Langerhans/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Proinsulin/biosynthesis</keyword><keyword>Protein Conformation</keyword><keyword>Ribosomes/metabolism</keyword></keywords><dates><year>1998</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-440X (Print) 0959-440X (Linking)</isbn><accession-num>9631292</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9631292</url></related-urls></urls></record></Cite></EndNote>3. Despite the variation in the amino acid sequence of insulin among species, certain segments of the molecule are highly conserved, such as the positions of the three disulphide bonds, both the ends of chain A and the C-terminal residues of chain B, resulting in the similar three-dimensional conformation of insulin among species.
Hence, insulin from one animal is very likely to be biologically active in other species. Indeed, pig insulin has been widely used to treat human patients.Biosynthesis:Insulin gene is located on the short arm of chromosome 11 and is expressed in ?-cells of the islets of Langerhans of the pancreas as a single polypeptide chain, preproinsulin. In the endoplasmic reticulum lumen, the signal polypeptide chain is cleaved and subsequently folded into its characteristic three-dimensional structure of proinsulin.
Secretory vesicles transfer proinsulin from the rough endoplasmic reticulum to the Golgi apparatus. In the immature storage vesicles formed from the Golgi, proinsulin is converted to insulin and C peptide. Further, the aqueous zinc and calcium-rich environment of the vesicles favours formation of zinc-containing proinsulin hexamers ADDIN EN.CITE <EndNote><Cite><Author>Dodson</Author><Year>1998</Year><RecNum>193</RecNum><DisplayText>3</DisplayText><record><rec-number>193</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>193</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Dodson, G.</author><author>Steiner, D.</author></authors></contributors><auth-address>National Institute of Medical Research, London, UK.
uk</auth-address><titles><title>The role of assembly in insulin's biosynthesis</title><secondary-title>Curr Opin Struct Biol</secondary-title><alt-title>Current opinion in structural biology</alt-title></titles><periodical><full-title>Curr Opin Struct Biol</full-title><abbr-1>Current opinion in structural biology</abbr-1></periodical><alt-periodical><full-title>Curr Opin Struct Biol</full-title><abbr-1>Current opinion in structural biology</abbr-1></alt-periodical><pages>189-94</pages><volume>8</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Biological Transport, Active</keyword><keyword>Cytoplasmic Granules/metabolism</keyword><keyword>Golgi Apparatus/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/*biosynthesis/*chemistry/genetics</keyword><keyword>Islets of Langerhans/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Proinsulin/biosynthesis</keyword><keyword>Protein Conformation</keyword><keyword>Ribosomes/metabolism</keyword></keywords><dates><year>1998</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0959-440X (Print) 0959-440X (Linking)</isbn><accession-num>9631292</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9631292</url></related-urls></urls></record></Cite></EndNote>3.
Bound to two zinc atoms, insulin is stored in granules as a hexamer and upon exocytosis, an equimolar ratio of insulin and C-peptide are released into the peripheral circulation.Biphasic Mode of insulin secretion:In response to a stimulus, primarily glucose, insulin is secreted from the islet ?-cells to the portal veins in a characteristic biphasic manner; with an initial rapid phase of insulin secretion, followed by a less intense but more sustained release phase of the hormone ADDIN EN.CITE <EndNote><Cite><Author>Bratanova-Tochkova</Author><Year>2002</Year><RecNum>195</RecNum><DisplayText>4</DisplayText><record><rec-number>195</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>195</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Bratanova-Tochkova, T. K.</author><author>Cheng, H.
</author><author>Daniel, S.</author><author>Gunawardana, S.</author><author>Liu, Y. J.</author><author>Mulvaney-Musa, J.</author><author>Schermerhorn, T.
</author><author>Straub, S. G.</author><author>Yajima, H.</author><author>Sharp, G. W.</author></authors></contributors><auth-address>Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York.</auth-address><titles><title>Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>S83-90</pages><volume>51 Suppl 1</volume><keywords><keyword>Animals</keyword><keyword>Insulin/*secretion</keyword><keyword>Islets of Langerhans/*metabolism/*secretion</keyword><keyword>Secretory Vesicles/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0012-1797 (Print) 0012-1797 (Linking)</isbn><accession-num>11815463</accession-num><urls><related-urls><url>http://www.ncbi.
nlm.nih.gov/pubmed/11815463</url></related-urls></urls></record></Cite></EndNote>4.
Increased levels of glucose induce the “first phase” of glucose-mediated insulin secretion. Glucose influx into the ?-cells enhances the ATP levels via coordinated glycolysis/TCA pathway. Elevated levels of cytoplasmic ATP/ADP ratio in ?-cell closes ATP-sensitive K+ channels (K+ATP channels) resulting in membrane depolarization and the influx of Ca2+ via L-type voltage-dependent Ca2+ channels (VDCC). Elevated cytosolic free Ca2+ concentration rapidly increases the rate of insulin exocytosis ADDIN EN.CITE <EndNote><Cite><Author>Soria</Author><Year>2004</Year><RecNum>196</RecNum><DisplayText>5</DisplayText><record><rec-number>196</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>196</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Soria, B.
</author><author>Quesada, I.</author><author>Ropero, A. B.</author><author>Pertusa, J. A.</author><author>Martin, F.</author><author>Nadal, A.</author></authors></contributors><auth-address>Institute of Bioengineering, Miguel Hernandez University, Alicante, Spain.
[email protected]</auth-address><titles><title>Novel players in pancreatic islet signaling: from membrane receptors to nuclear channels</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>S86-91</pages><volume>53 Suppl 1</volume><keywords><keyword>Animals</keyword><keyword>Gene Expression Regulation</keyword><keyword>Glucose/pharmacology</keyword><keyword>Humans</keyword><keyword>Ion Channels/*physiology</keyword><keyword>Islets of Langerhans/drug effects/*physiology</keyword><keyword>Models, Biological</keyword><keyword>Receptors, Cell Surface/*physiology</keyword><keyword>Receptors, Cytoplasmic and Nuclear/*physiology</keyword><keyword>Signal Transduction/*physiology</keyword></keywords><dates><year>2004</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0012-1797 (Print) 0012-1797 (Linking)</isbn><accession-num>14749271</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.
gov/pubmed/14749271</url></related-urls></urls></record></Cite></EndNote>5. However, glucose augments insulin exocytosis induced by K+ depolarization even when the K+ATP channels are fully open or closed in the presence of diazoxide or sulfonylureas, respectively; indicating the presence of both a K+ ATP channel-independent Ca2+-dependent pathway and K+ATP channel-independent Ca2+-independent pathways for insulin secretion 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ADDIN EN.CITE 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ADDIN EN.
CITE.DATA 6, 7. Other mediators that potentiate insulin secretion include activation of phospholipases and protein kinase C, stimulation of adenylyl cyclase activity and activation of ? cell protein kinase A. This latter enzymatic activity may be triggered by hormones, such as GLP-1 and GIP. These hormonal inducing signalling appears to play a significant role in the second phase of glucose-mediated insulin secretion, after refilling of secretory granules translocated from reserve pools ADDIN EN.
CITE <EndNote><Cite><Author>Bratanova-Tochkova</Author><Year>2002</Year><RecNum>195</RecNum><DisplayText>4</DisplayText><record><rec-number>195</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>195</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Bratanova-Tochkova, T. K.</author><author>Cheng, H.
</author><author>Daniel, S.</author><author>Gunawardana, S.</author><author>Liu, Y. J.</author><author>Mulvaney-Musa, J.</author><author>Schermerhorn, T.</author><author>Straub, S.
G.</author><author>Yajima, H.</author><author>Sharp, G. W.
</author></authors></contributors><auth-address>Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York.</auth-address><titles><title>Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>S83-90</pages><volume>51 Suppl 1</volume><keywords><keyword>Animals</keyword><keyword>Insulin/*secretion</keyword><keyword>Islets of Langerhans/*metabolism/*secretion</keyword><keyword>Secretory Vesicles/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0012-1797 (Print) 0012-1797 (Linking)</isbn><accession-num>11815463</accession-num><urls><related-urls><url>http://www.ncbi.
nlm.nih.gov/pubmed/11815463</url></related-urls></urls></record></Cite></EndNote>4.It has long been considered that there are distinct pools of insulin granules known as readily releasable pools (RRP) and reserve pools (RP). In the biphasic GSIS, initial rapid insulin exocytosis from the RRP that occurs by the K+ATP-dependent mechanism, the second phase of gradual enhancement of amplification is indicated by the K+ATP independent signal. The latter can occur with replenishment of the RRP from the RP, so the biphasic insulin release as ‘fusion and replenishment’ is proposed ADDIN EN.CITE <EndNote><Cite><Author>Bratanova-Tochkova</Author><Year>2002</Year><RecNum>195</RecNum><DisplayText>4</DisplayText><record><rec-number>195</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>195</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Bratanova-Tochkova, T.
K.</author><author>Cheng, H.</author><author>Daniel, S.</author><author>Gunawardana, S.</author><author>Liu, Y. J.</author><author>Mulvaney-Musa, J.</author><author>Schermerhorn, T.
</author><author>Straub, S. G.</author><author>Yajima, H.
</author><author>Sharp, G. W.</author></authors></contributors><auth-address>Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York.</auth-address><titles><title>Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>S83-90</pages><volume>51 Suppl 1</volume><keywords><keyword>Animals</keyword><keyword>Insulin/*secretion</keyword><keyword>Islets of Langerhans/*metabolism/*secretion</keyword><keyword>Secretory Vesicles/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0012-1797 (Print) 0012-1797 (Linking)</isbn><accession-num>11815463</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11815463</url></related-urls></urls></record></Cite></EndNote>4.
Factors influencing Insulin Secretion: Secretion of insulin at physiological level is regulated by a complex interplay of numerous events as discussed below. Incretins: Incretin hormones are released in a fed state from gut enteroendocrine cells. They potentiate nutrient-induced insulin secretion for up to 70% postprandial. These hormones include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), both known to promote proliferation/neogenesis of ?- cells and prevent their apoptosis. They regulate insulin secretion from food intake and their effects are progressively amplified with direct correlation with plasma glucose concentration.
Mechanistically, incretins bind to the G protein-coupled receptors on the ?-cell membrane and increase cellular 3?,5?-cyclic adenosine monophosphate (cAMP) levels which in turn enhances GSIS through protein kinase A (PKA)-dependent and -independent mechanisms ADDIN EN.CITE <EndNote><Cite><Author>Seino</Author><Year>2005</Year><RecNum>199</RecNum><DisplayText>8</DisplayText><record><rec-number>199</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>199</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Seino, S.</author><author>Shibasaki, T.</author></authors></contributors><auth-address>Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. seino@med.
kobe-u.ac.jp</auth-address><titles><title>PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis</title><secondary-title>Physiol Rev</secondary-title><alt-title>Physiological reviews</alt-title></titles><periodical><full-title>Physiol Rev</full-title><abbr-1>Physiological reviews</abbr-1></periodical><alt-periodical><full-title>Physiol Rev</full-title><abbr-1>Physiological reviews</abbr-1></alt-periodical><pages>1303-42</pages><volume>85</volume><number>4</number><keywords><keyword>Action Potentials</keyword><keyword>Animals</keyword><keyword>Cyclic AMP/antagonists & inhibitors/*physiology</keyword><keyword>Cyclic AMP-Dependent Protein Kinases/*physiology</keyword><keyword>Endocrine Glands/physiology</keyword><keyword>Exocrine Glands/physiology</keyword><keyword>Exocytosis/*physiology</keyword><keyword>Humans</keyword><keyword>Neurons/physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0031-9333 (Print) 0031-9333 (Linking)</isbn><accession-num>16183914</accession-num><urls><related-urls><url>http://www.
ncbi.nlm.nih.
gov/pubmed/16183914</url></related-urls></urls><electronic-resource-num>10.1152/physrev.00001.2005</electronic-resource-num></record></Cite></EndNote>8. Amino acids: Both acute and chronic phases of insulin secretion are regulated by few specific amino acids. Four amino acids namely leucine, isoleucine, alanine, and arginine play a significant role in stimulating electrical activities in ?-cell requires for insulin secretion ADDIN EN.CITE <EndNote><Cite><Author>Newsholme</Author><Year>2005</Year><RecNum>200</RecNum><DisplayText>9</DisplayText><record><rec-number>200</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>200</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Newsholme, P.
</author><author>Brennan, L.</author><author>Rubi, B.</author><author>Maechler, P.
</author></authors></contributors><auth-address>Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. [email protected]</auth-address><titles><title>New insights into amino acid metabolism, beta-cell function and diabetes</title><secondary-title>Clin Sci (Lond)</secondary-title><alt-title>Clinical science</alt-title></titles><periodical><full-title>Clin Sci (Lond)</full-title><abbr-1>Clinical science</abbr-1></periodical><alt-periodical><full-title>Clin Sci (Lond)</full-title><abbr-1>Clinical science</abbr-1></alt-periodical><pages>185-94</pages><volume>108</volume><number>3</number><keywords><keyword>Amino Acids/*metabolism</keyword><keyword>Calcium/metabolism</keyword><keyword>Diabetes Mellitus/*metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/*secretion</keyword><keyword>Islets of Langerhans/*metabolism/secretion</keyword><keyword>Mitochondria/metabolism</keyword><keyword>Signal Transduction/*physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0143-5221 (Print) 0143-5221 (Linking)</isbn><accession-num>15544573</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15544573</url></related-urls></urls><electronic-resource-num>10.
1042/CS20040290</electronic-resource-num></record></Cite></EndNote>9. Arginine and Alanine stimulate insulin secretion 2-10 minutes after intravenous injection by increasing the permeability of K+ ion channels leading to depolarization of membrane and opening of Ca2+ channels ADDIN EN.CITE <EndNote><Cite><Author>Wilcox</Author><Year>2005</Year><RecNum>632</RecNum><DisplayText>10</DisplayText><record><rec-number>632</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>632</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Wilcox, G.</author></authors></contributors><auth-address>Melbourne Pathology, Collingwood, VIC 3066, Australia. [email protected].
edu.au</auth-address><titles><title>Insulin and insulin resistance</title><secondary-title>Clin Biochem Rev</secondary-title><alt-title>The Clinical biochemist. Reviews</alt-title></titles><periodical><full-title>Clin Biochem Rev</full-title><abbr-1>The Clinical biochemist. Reviews</abbr-1></periodical><alt-periodical><full-title>Clin Biochem Rev</full-title><abbr-1>The Clinical biochemist. Reviews</abbr-1></alt-periodical><pages>19-39</pages><volume>26</volume><number>2</number><dates><year>2005</year><pub-dates><date>May</date></pub-dates></dates><isbn>0159-8090 (Print) 0159-8090 (Linking)</isbn><accession-num>16278749</accession-num><urls><related-urls><url>http://www.ncbi.nlm.
nih.gov/pubmed/16278749</url></related-urls></urls><custom2>1204764</custom2></record></Cite></EndNote>10. Whereas, Leucine and isoleucine enhance insulin secretion by increasing the concentration of ATP generation through Kreb Cycle ADDIN EN.
CITE <EndNote><Cite><Author>Wilcox</Author><Year>2005</Year><RecNum>632</RecNum><DisplayText>10</DisplayText><record><rec-number>632</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>632</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Wilcox, G.</author></authors></contributors><auth-address>Melbourne Pathology, Collingwood, VIC 3066, Australia. gisela.wilcox@med.
monash.edu.au</auth-address><titles><title>Insulin and insulin resistance</title><secondary-title>Clin Biochem Rev</secondary-title><alt-title>The Clinical biochemist.
Reviews</alt-title></titles><periodical><full-title>Clin Biochem Rev</full-title><abbr-1>The Clinical biochemist. Reviews</abbr-1></periodical><alt-periodical><full-title>Clin Biochem Rev</full-title><abbr-1>The Clinical biochemist. Reviews</abbr-1></alt-periodical><pages>19-39</pages><volume>26</volume><number>2</number><dates><year>2005</year><pub-dates><date>May</date></pub-dates></dates><isbn>0159-8090 (Print) 0159-8090 (Linking)</isbn><accession-num>16278749</accession-num><urls><related-urls><url>http://www.ncbi.nlm.
nih.gov/pubmed/16278749</url></related-urls></urls><custom2>1204764</custom2></record></Cite></EndNote>10.Free fatty acid (FFA): FFAs are important for normal functioning of pancreatic ?-cells however, a chronic excess of FFAs particularly saturated FFAs cause lipotoxicity which is associated with induction of insulin resistance ADDIN EN.
CITE <EndNote><Cite><Author>Boden</Author><Year>2005</Year><RecNum>201</RecNum><DisplayText>11</DisplayText><record><rec-number>201</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>201</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Boden, G.</author></authors></contributors><auth-address>Division of Endocrinology/Diabetes/Metabolism, Temple University School of Medicine, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140, USA. bodengh@tuhs.
temple.edu</auth-address><titles><title>Free fatty acids and insulin secretion in humans</title><secondary-title>Curr Diab Rep</secondary-title><alt-title>Current diabetes reports</alt-title></titles><periodical><full-title>Curr Diab Rep</full-title><abbr-1>Current diabetes reports</abbr-1></periodical><alt-periodical><full-title>Curr Diab Rep</full-title><abbr-1>Current diabetes reports</abbr-1></alt-periodical><pages>167-70</pages><volume>5</volume><number>3</number><keywords><keyword>Diabetes Mellitus, Type 2/epidemiology/prevention & control</keyword><keyword>Fatty Acids, Nonesterified/*blood/*pharmacology</keyword><keyword>Humans</keyword><keyword>Insulin/blood/*secretion</keyword><keyword>Prediabetic State/blood</keyword></keywords><dates><year>2005</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1534-4827 (Print) 1534-4827 (Linking)</isbn><accession-num>15929861</accession-num><urls><related-urls><url>http://www.ncbi.
nlm.nih.gov/pubmed/15929861</url></related-urls></urls></record></Cite></EndNote>11. Yet, short-term (hours) exposure at the physiological concentration of FFA augments GSIS independent of K+ATP channel 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 12, 13.
An agonist of GPR40, the membrane receptor for FFA, elevates intracellular Ca2+ levels through activation of phospholipase C and protein kinase D1 and thus resulting in exocytosis on insulin granules ADDIN EN.CITE <EndNote><Cite><Author>Kaku</Author><Year>2013</Year><RecNum>204</RecNum><DisplayText>14</DisplayText><record><rec-number>204</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>204</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Kaku, K.</author><author>Araki, T.</author><author>Yoshinaka, R.
</author></authors></contributors><auth-address>Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Okayama, Japan. [email protected]</auth-address><titles><title>Randomized, double-blind, dose-ranging study of TAK-875, a novel GPR40 agonist, in Japanese patients with inadequately controlled type 2 diabetes</title><secondary-title>Diabetes Care</secondary-title><alt-title>Diabetes care</alt-title></titles><periodical><full-title>Diabetes Care</full-title><abbr-1>Diabetes care</abbr-1></periodical><alt-periodical><full-title>Diabetes Care</full-title><abbr-1>Diabetes care</abbr-1></alt-periodical><pages>245-50</pages><volume>36</volume><number>2</number><keywords><keyword>Aged</keyword><keyword>Asian Continental Ancestry Group</keyword><keyword>Benzofurans/adverse effects/*therapeutic use</keyword><keyword>Diabetes Mellitus, Type 2/*drug therapy</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Receptors, G-Protein-Coupled/*antagonists & inhibitors</keyword><keyword>Sulfones/adverse effects/*therapeutic use</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1935-5548 (Electronic) 0149-5992 (Linking)</isbn><accession-num>23086138</accession-num><urls><related-urls><url>http://www.
ncbi.nlm.nih.gov/pubmed/23086138</url></related-urls></urls><custom2>3554318</custom2><electronic-resource-num>10.
2337/dc12-0872</electronic-resource-num></record></Cite></EndNote>14. Parasympathetic Nerves and Neuropeptides: Neuroendocrine regulation of insulin secretion has been proposed, however, the molecular insights are still emerging. Preliminary activation of the parasympathetic nervous system in response to food enhances cephalic phase of insulin secretion. Here, acetylcholine binds to the cholinergic muscarinic receptors on islet cells leading to hydrolysis of phospholipids, accumulation of cellular inositol 1, 4, 5-triphosphate thereby activating PKC, resulting in enhanced GSIS ADDIN EN.CITE <EndNote><Cite><Author>Gilon</Author><Year>2001</Year><RecNum>206</RecNum><DisplayText>15</DisplayText><record><rec-number>206</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>206</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Gilon, P.
</author><author>Henquin, J. C.</author></authors></contributors><auth-address>Unite d'Endocrinologie et Metabolisme, University of Louvain Faculty of Medicine, B-1200 Brussels, Belgium. [email protected].
ac.be</auth-address><titles><title>Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function</title><secondary-title>Endocr Rev</secondary-title><alt-title>Endocrine reviews</alt-title></titles><periodical><full-title>Endocr Rev</full-title><abbr-1>Endocrine reviews</abbr-1></periodical><alt-periodical><full-title>Endocr Rev</full-title><abbr-1>Endocrine reviews</abbr-1></alt-periodical><pages>565-604</pages><volume>22</volume><number>5</number><keywords><keyword>Acetylcholine/pharmacology</keyword><keyword>Animals</keyword><keyword>Cholinergic Fibers/*physiology</keyword><keyword>Humans</keyword><keyword>Insulin/secretion</keyword><keyword>Islets of Langerhans/drug effects/innervation/*physiology</keyword><keyword>Parasympathetic Nervous System/physiology</keyword><keyword>Sympathetic Nervous System/physiology</keyword></keywords><dates><year>2001</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0163-769X (Print) 0163-769X (Linking)</isbn><accession-num>11588141</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.
gov/pubmed/11588141</url></related-urls></urls><electronic-resource-num>10.1210/edrv.22.
5.0440</electronic-resource-num></record></Cite></EndNote>15. Similarly, pituitary adenylate cyclase-activating polypeptide (PACAP) and ?-adrenoceptors, also enhances insulin secretion at the picomolar range by increasing cellular cAMP 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ADDIN EN.CITE.DATA 16. Interestingly, the mechanism is shunted during fasting or under low plasma glucose state. Conversely, during stress, sympathetic nervous system suppresses insulin secretion by increasing noradrenaline.
Noradrenaline binds to the ?2-adrenergic receptor and activates the heterotrimeric G protein which activates the K+ ATP channels resulting in inhibition of Ca2+ channel and insulin secretion 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 17. Also, Somatostatin, secreted from pancreatic ?-cells, suppresses insulin secretion by binding to the specific heterotrimeric G protein-coupled receptor. Thus, insulin secretion is a complex multifactorial event that is finely tuned by a variety of stimulatory and inhibitory signals produced in response to nutrients, hormones and neural inputs (Figure 1.
1). Insulin signalling: Insulin signalling triggers the uptake of glucose, fatty acids, and amino acids into the liver, adipose and skeletal muscle promoting storage of these nutrients. Insulin signalling is triggered by binding of insulin to the extracellular domains on insulin receptor (Figure 1.2). The insulin receptor is composed of two extracellular domains: two alpha subunits (?-subunits) and two Beta transmembrane subunits (?-subunits). Binding of insulin to the ?-subunits of insulin receptor induces a conformational change which leads to activation of the kinase activity in the ?-subunits resulting in trans-phosphorylation between ?-subunits that allows the recruitment and activation of insulin receptor substrate (IRS) proteins, subsequently. Activated receptor phosphorylates IRS at multiple tyrosine residues that form binding sites for intracellular molecules that contain Src-homology2 (SH2) domains such as PI3-kinase (PI3K).
PI3K, by two SH2 domains in its regulatory subunits, binds to the phospho-tyrosine sites on IRS leading to the activation of its catalytic subunit, which then rapidly phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to the lipid second messenger phosphatidylinositol (3,4,5)-triphosphate (PIP3) at the plasma membrane.Membrane-bound activated PIP3 recruits and activates PDK-1 (3-phosphoinositide-dependent protein kinase 1) that acts as the major upstream kinase responsible for the phosphorylation and activation of the downstream AGC kinases. PDK1 phosphorylates and activates the crucial insulin responsive AGC protein kinase Akt, at Thr308 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ADDIN EN.CITE 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ADDIN EN.CITE.
DATA 18. However, for full activation, Akt needs to be phosphorylated at Ser473 in its hydrophobic pocket which is accomplished by the mammalian target of rapamycin complex 2 (mTORC2) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 19, 20.Insulin signalling through Akt: Based on numerous clinical and biochemical studies, it is clear that Akt signalling plays a central role in insulin-stimulated glucose uptake in both skeletal muscle and adipose while inhibiting hepatic glucose output from the liver. Insulin activated Akt phosphorylates a number of downstream substrates at Ser/Thr residues which carry out a wide variety of functions such as glucose absorption and its utilization, as well as the synthesis of glycogen, protein, and lipid in response to insulin. Apart from Akt, the role of atypical PKCs and SH2 domain proteins such as Grb2 and Shc in mediating the action of insulin are also well reported and are discussed in brief later.
Role of Akt in transcription & Lipid biosynthesis: The Forkhead box O (Foxo) family are transcription factors that control the expression of lipogenic and gluconeogenic genes. Akt blocks the transcriptional activity of FoxO protein by phosphorylating it at several sites which provides docking sites for the binding 14-3-3 family of proteins, thereby excluding FoxO from the nucleus ADDIN EN.CITE <EndNote><Cite><Author>Tzivion</Author><Year>2011</Year><RecNum>216</RecNum><DisplayText>21</DisplayText><record><rec-number>216</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>216</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Tzivion, G.</author><author>Dobson, M.</author><author>Ramakrishnan, G.</author></authors></contributors><auth-address>Cancer Institute and Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS 39216, USA. [email protected]</auth-address><titles><title>FoxO transcription factors; Regulation by AKT and 14-3-3 proteins</title><secondary-title>Biochim Biophys Acta</secondary-title><alt-title>Biochimica et biophysica acta</alt-title></titles><periodical><full-title>Biochim Biophys Acta</full-title><abbr-1>Biochimica et biophysica acta</abbr-1></periodical><alt-periodical><full-title>Biochim Biophys Acta</full-title><abbr-1>Biochimica et biophysica acta</abbr-1></alt-periodical><pages>1938-45</pages><volume>1813</volume><number>11</number><keywords><keyword>14-3-3 Proteins/*metabolism</keyword><keyword>Animals</keyword><keyword>Forkhead Box Protein O1</keyword><keyword>Forkhead Box Protein O3</keyword><keyword>Forkhead Transcription Factors/*metabolism</keyword><keyword>Humans</keyword><keyword>Protein Binding</keyword><keyword>Proto-Oncogene Proteins c-akt/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-mdm2/metabolism</keyword><keyword>Transcription Factors/metabolism</keyword></keywords><dates><year>2011</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0006-3002 (Print) 0006-3002 (Linking)</isbn><accession-num>21708191</accession-num><urls><related-urls><url>http://www.
ncbi.nlm.nih.gov/pubmed/21708191</url></related-urls></urls><electronic-resource-num>10.1016/j.bbamcr.2011.06.
002</electronic-resource-num></record></Cite></EndNote>21. Further, Akt-dependent phosphorylation of PGC-1? impairs its ability to promote gluconeogenesis and fatty acid oxidation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 22 and Akt mediated activating phosphorylation of phosphodiesterase 3B (PDE3B) results in a decrease in cAMP levels 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 23, which plays important roles in insulin facilitated inhibition of lipolysis in adipocytes and insulin secretion in ? cells 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ADDIN EN.
CITE 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 ADDIN EN.CITE.DATA 24 . Role of Akt in glucose uptake: The impact of Akt in augmenting glucose uptake from peripheral circulation has been studied in all insulin-sensitive organs: Liver, Muscle, and Adipose. It is well established that glucose absorption from circulation is mediated by GLUT4 (Glucose Transporter 4). Among the three Akt isoforms, Akt2 is primarily involved in insulin-stimulated GLUT4 translocation.
Preliminary studies suggest that the GTPase-activating protein Akt substrate of 160 kDa (AS160), also called TBC1D4 (TBC1 Domain Family Member 4), and its homolog TBC1D1, which are substrates of Akt are directly involved in regulating GLUT4 translocation in insulin and contraction-mediated glucose uptake <EndNote><Cite><Author>Sano</Author><Year>2003</Year><RecNum>220</RecNum><DisplayText>[25-28]</DisplayText><record><rec-number>220</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">220</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sano, H.</author><author>Kane, S.</author><author>Sano, E.</author><author>Miinea, C. P.</author><author>Asara, J. M.</author><author>Lane, W. S.</author><author>Garner, C. W.</author><author>Lienhard, G. E.</author></authors></contributors><auth-address>Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.</auth-address><titles><title>Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>14599-602</pages><volume>278</volume><number>17</number><keywords><keyword>3T3 Cells</keyword><keyword>Animals</keyword><keyword>Binding Sites</keyword><keyword>GTPase-Activating Proteins/genetics/*metabolism</keyword><keyword>Glucose Transporter Type 4</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Mice</keyword><keyword>Microscopy, Fluorescence</keyword><keyword>Monosaccharide Transport Proteins/*metabolism</keyword><keyword>*Muscle Proteins</keyword><keyword>Mutation</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein Structure, Tertiary</keyword><keyword>rab GTP-Binding Proteins/*metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Apr 25</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>12637568</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12637568</url></related-urls></urls><electronic-resource-num>10.1074/jbc.C300063200</electronic-resource-num></record></Cite><Cite><Author>Sakamoto</Author><Year>2008</Year><RecNum>221</RecNum><record><rec-number>221</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">221</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sakamoto, K.</author><author>Holman, G. D.</author></authors></contributors><auth-address>MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow St., Dundee, DD1 5EH, UK. k.sakamoto@dundee.ac.uk</auth-address><titles><title>Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic</title><secondary-title>Am J Physiol Endocrinol Metab</secondary-title><alt-title>American journal of physiology. Endocrinology and metabolism</alt-title></titles><periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></alt-periodical><pages>E29-37</pages><volume>295</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>GTPase-Activating Proteins/*metabolism</keyword><keyword>Glucose Transporter Type 4/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Muscle Contraction/physiology</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0193-1849 (Print)&#xD;0193-1849 (Linking)</isbn><accession-num>18477703</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18477703</url></related-urls></urls><custom2>2493596</custom2><electronic-resource-num>10.1152/ajpendo.90331.2008</electronic-resource-num></record></Cite><Cite><Author>Taylor</Author><Year>2008</Year><RecNum>222</RecNum><record><rec-number>222</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">222</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taylor, E. B.</author><author>An, D.</author><author>Kramer, H. F.</author><author>Yu, H.</author><author>Fujii, N. L.</author><author>Roeckl, K. S.</author><author>Bowles, N.</author><author>Hirshman, M. F.</author><author>Xie, J.</author><author>Feener, E. P.</author><author>Goodyear, L. J.</author></authors></contributors><auth-address>The Joslin Diabetes Center Section on Metabolism and Proteomics Core and Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.</auth-address><titles><title>Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>9787-96</pages><volume>283</volume><number>15</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Amino Acid Motifs/genetics</keyword><keyword>Aminoimidazole Carboxamide/*analogs &amp; derivatives/pharmacology</keyword><keyword>Animals</keyword><keyword>Cyclic AMP-Dependent Protein Kinases/genetics/metabolism</keyword><keyword>Enzyme Activation/drug effects</keyword><keyword>GTPase-Activating Proteins/genetics/metabolism</keyword><keyword>Gene Expression Regulation/drug effects/physiology</keyword><keyword>Glucose/metabolism</keyword><keyword>Glucose Transporter Type 4/genetics/metabolism</keyword><keyword>Hypoglycemic Agents/*pharmacology</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred ICR</keyword><keyword>Muscle Contraction/*drug effects/physiology</keyword><keyword>Muscle Proteins/genetics/*metabolism</keyword><keyword>Muscle, Skeletal/*metabolism</keyword><keyword>Nuclear Proteins/genetics/*metabolism</keyword><keyword>Organ Specificity/physiology</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein Transport/drug effects/physiology</keyword><keyword>Proto-Oncogene Proteins c-akt/genetics/metabolism</keyword><keyword>Ribonucleotides/*pharmacology</keyword></keywords><dates><year>2008</year><pub-dates><date>Apr 11</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>18276596</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18276596</url></related-urls></urls><custom2>2442306</custom2><electronic-resource-num>10.1074/jbc.M708839200</electronic-resource-num></record></Cite><Cite><Author>An</Author><Year>2010</Year><RecNum>223</RecNum><record><rec-number>223</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">223</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>An, D.</author><author>Toyoda, T.</author><author>Taylor, E. B.</author><author>Yu, H.</author><author>Fujii, N.</author><author>Hirshman, M. F.</author><author>Goodyear, L. J.</author></authors></contributors><auth-address>Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.</auth-address><titles><title>TBC1D1 regulates insulin- and contraction-induced glucose transport in mouse skeletal muscle</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>1358-65</pages><volume>59</volume><number>6</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/physiology</keyword><keyword>Animals</keyword><keyword>Biological Transport/physiology</keyword><keyword>DNA Primers</keyword><keyword>DNA, Complementary/genetics</keyword><keyword>GTPase-Activating Proteins</keyword><keyword>Gene Expression Regulation</keyword><keyword>Glucose/*metabolism</keyword><keyword>Glucose Transporter Type 4/metabolism</keyword><keyword>Insulin/pharmacology/*physiology</keyword><keyword>Mice</keyword><keyword>Muscle Contraction/drug effects/*physiology</keyword><keyword>Muscle, Skeletal/drug effects/*physiology</keyword><keyword>Mutation</keyword><keyword>Nuclear Proteins/*genetics/physiology</keyword><keyword>Obesity/genetics/physiopathology</keyword><keyword>Polymerase Chain Reaction</keyword></keywords><dates><year>2010</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1939-327X (Electronic)&#xD;0012-1797 (Linking)</isbn><accession-num>20299473</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20299473</url></related-urls></urls><custom2>2874696</custom2><electronic-resource-num>10.2337/db09-1266</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Sano</Author><Year>2003</Year><RecNum>220</RecNum><DisplayText>[25-28]</DisplayText><record><rec-number>220</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">220</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sano, H.</author><author>Kane, S.</author><author>Sano, E.</author><author>Miinea, C. P.</author><author>Asara, J. M.</author><author>Lane, W. S.</author><author>Garner, C. W.</author><author>Lienhard, G. E.</author></authors></contributors><auth-address>Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.</auth-address><titles><title>Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>14599-602</pages><volume>278</volume><number>17</number><keywords><keyword>3T3 Cells</keyword><keyword>Animals</keyword><keyword>Binding Sites</keyword><keyword>GTPase-Activating Proteins/genetics/*metabolism</keyword><keyword>Glucose Transporter Type 4</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Mice</keyword><keyword>Microscopy, Fluorescence</keyword><keyword>Monosaccharide Transport Proteins/*metabolism</keyword><keyword>*Muscle Proteins</keyword><keyword>Mutation</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein Structure, Tertiary</keyword><keyword>rab GTP-Binding Proteins/*metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Apr 25</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>12637568</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12637568</url></related-urls></urls><electronic-resource-num>10.1074/jbc.C300063200</electronic-resource-num></record></Cite><Cite><Author>Sakamoto</Author><Year>2008</Year><RecNum>221</RecNum><record><rec-number>221</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">221</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sakamoto, K.</author><author>Holman, G. D.</author></authors></contributors><auth-address>MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow St., Dundee, DD1 5EH, UK. k.sakamoto@dundee.ac.uk</auth-address><titles><title>Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic</title><secondary-title>Am J Physiol Endocrinol Metab</secondary-title><alt-title>American journal of physiology. Endocrinology and metabolism</alt-title></titles><periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></alt-periodical><pages>E29-37</pages><volume>295</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>GTPase-Activating Proteins/*metabolism</keyword><keyword>Glucose Transporter Type 4/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Muscle Contraction/physiology</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0193-1849 (Print)&#xD;0193-1849 (Linking)</isbn><accession-num>18477703</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18477703</url></related-urls></urls><custom2>2493596</custom2><electronic-resource-num>10.1152/ajpendo.90331.2008</electronic-resource-num></record></Cite><Cite><Author>Taylor</Author><Year>2008</Year><RecNum>222</RecNum><record><rec-number>222</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">222</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taylor, E. B.</author><author>An, D.</author><author>Kramer, H. F.</author><author>Yu, H.</author><author>Fujii, N. L.</author><author>Roeckl, K. S.</author><author>Bowles, N.</author><author>Hirshman, M. F.</author><author>Xie, J.</author><author>Feener, E. P.</author><author>Goodyear, L. J.</author></authors></contributors><auth-address>The Joslin Diabetes Center Section on Metabolism and Proteomics Core and Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.</auth-address><titles><title>Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>9787-96</pages><volume>283</volume><number>15</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Amino Acid Motifs/genetics</keyword><keyword>Aminoimidazole Carboxamide/*analogs &amp; derivatives/pharmacology</keyword><keyword>Animals</keyword><keyword>Cyclic AMP-Dependent Protein Kinases/genetics/metabolism</keyword><keyword>Enzyme Activation/drug effects</keyword><keyword>GTPase-Activating Proteins/genetics/metabolism</keyword><keyword>Gene Expression Regulation/drug effects/physiology</keyword><keyword>Glucose/metabolism</keyword><keyword>Glucose Transporter Type 4/genetics/metabolism</keyword><keyword>Hypoglycemic Agents/*pharmacology</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred ICR</keyword><keyword>Muscle Contraction/*drug effects/physiology</keyword><keyword>Muscle Proteins/genetics/*metabolism</keyword><keyword>Muscle, Skeletal/*metabolism</keyword><keyword>Nuclear Proteins/genetics/*metabolism</keyword><keyword>Organ Specificity/physiology</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein Transport/drug effects/physiology</keyword><keyword>Proto-Oncogene Proteins c-akt/genetics/metabolism</keyword><keyword>Ribonucleotides/*pharmacology</keyword></keywords><dates><year>2008</year><pub-dates><date>Apr 11</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>18276596</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18276596</url></related-urls></urls><custom2>2442306</custom2><electronic-resource-num>10.1074/jbc.M708839200</electronic-resource-num></record></Cite><Cite><Author>An</Author><Year>2010</Year><RecNum>223</RecNum><record><rec-number>223</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">223</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>An, D.</author><author>Toyoda, T.</author><author>Taylor, E. B.</author><author>Yu, H.</author><author>Fujii, N.</author><author>Hirshman, M. F.</author><author>Goodyear, L. J.</author></authors></contributors><auth-address>Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.</auth-address><titles><title>TBC1D1 regulates insulin- and contraction-induced glucose transport in mouse skeletal muscle</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>1358-65</pages><volume>59</volume><number>6</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/physiology</keyword><keyword>Animals</keyword><keyword>Biological Transport/physiology</keyword><keyword>DNA Primers</keyword><keyword>DNA, Complementary/genetics</keyword><keyword>GTPase-Activating Proteins</keyword><keyword>Gene Expression Regulation</keyword><keyword>Glucose/*metabolism</keyword><keyword>Glucose Transporter Type 4/metabolism</keyword><keyword>Insulin/pharmacology/*physiology</keyword><keyword>Mice</keyword><keyword>Muscle Contraction/drug effects/*physiology</keyword><keyword>Muscle, Skeletal/drug effects/*physiology</keyword><keyword>Mutation</keyword><keyword>Nuclear Proteins/*genetics/physiology</keyword><keyword>Obesity/genetics/physiopathology</keyword><keyword>Polymerase Chain Reaction</keyword></keywords><dates><year>2010</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1939-327X (Electronic)&#xD;0012-1797 (Linking)</isbn><accession-num>20299473</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20299473</url></related-urls></urls><custom2>2874696</custom2><electronic-resource-num>10.2337/db09-1266</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 25-28. Upon insulin stimulus, Akt phosphorylates and deactivates AS160 resulting in translocation of GLUT4 to the periphery by reducing the “tethering” of the vesicle, by proteins called TUG and also by increasing the activity of Rab proteins which stimulates the translocation of these vesicles containing GLUT4 to the periphery ADDIN EN.
CITE <EndNote><Cite><Author>Leney</Author><Year>2009</Year><RecNum>208</RecNum><DisplayText>29</DisplayText><record><rec-number>208</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>208</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Leney, S. E.</author><author>Tavare, J. M.
</author></authors></contributors><auth-address>Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.</auth-address><titles><title>The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets</title><secondary-title>J Endocrinol</secondary-title><alt-title>The Journal of endocrinology</alt-title></titles><periodical><full-title>J Endocrinol</full-title><abbr-1>The Journal of endocrinology</abbr-1></periodical><alt-periodical><full-title>J Endocrinol</full-title><abbr-1>The Journal of endocrinology</abbr-1></alt-periodical><pages>1-18</pages><volume>203</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Cell Membrane/metabolism</keyword><keyword>Diabetes Mellitus/drug therapy/metabolism</keyword><keyword>Glucose/*metabolism</keyword><keyword>Glucose Transporter Type 4/*metabolism</keyword><keyword>Homeostasis</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2009</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1479-6805 (Electronic) 0022-0795 (Linking)</isbn><accession-num>19389739</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19389739</url></related-urls></urls><electronic-resource-num>10.1677/JOE-09-0037</electronic-resource-num></record></Cite></EndNote>29. Role of Akt in protein synthesis: Apart from regulating metabolism, insulin also plays a dominant role in promoting cellular proliferation. Hence it was speculated that Akt can regulate the protein translational machinery activity, most energy consuming biosynthetic machinery of the cell. One of the key regulators of transcriptional, translational, and post-translational mechanisms activated downstream of PI3K is the protein kinase complex, the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1). mTORC1 consists of the core subunits mTOR, a regulatory-associated protein of mTOR (Raptor), and mammalian lethal with SEC13 protein 8 (mLST8), plus two endogenous inhibitors of the complex, 40kDa Proline-rich Akt substrate (PRAS40) and DEP domain-containing mTOR-interacting protein (DEPTOR) ADDIN EN.CITE <EndNote><Cite><Author>Laplante</Author><Year>2012</Year><RecNum>210</RecNum><DisplayText>30</DisplayText><record><rec-number>210</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>210</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Laplante, M.</author><author>Sabatini, D. M.</author></authors></contributors><auth-address>Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.</auth-address><titles><title>mTOR signaling in growth control and disease</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>274-93</pages><volume>149</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Humans</keyword><keyword>Metabolic Diseases/metabolism</keyword><keyword>Neoplasms/metabolism</keyword><keyword>Neurodegenerative Diseases/metabolism</keyword><keyword>*Signal Transduction</keyword><keyword>Stem Cells/metabolism</keyword><keyword>TOR Serine-Threonine Kinases/*metabolism</keyword></keywords><dates><year>2012</year><pub-dates><date>Apr 13</date></pub-dates></dates><isbn>1097-4172 (Electronic) 0092-8674 (Linking)</isbn><accession-num>22500797</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22500797</url></related-urls></urls><custom2>3331679</custom2><electronic-resource-num>10.1016/j.cell.2012.03.017</electronic-resource-num></record></Cite></EndNote>30. It is proposed that Akt inhibits the TSC (Tuberous sclerosis proteins) complex, the specific GAP for the small GTPase Rheb, through multi-site phosphorylation of the TSC2 subunit which relieves inhibition of Rheb, allowing it to become activate and stimulate mTORC1 kinase activity. Once mTORC1 is activated by RHEB, the simultaneous phosphorylation of its inhibitory subunit PRAS40 by Akt and mTORC1 itself causes PRAS40 to dissociate from mTORC1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 31. Mechanistically, mTORC1 complex upon activation phosphorylates 4E-binding protein 1 (4E-BP1) which hampers its interaction with eIF4E (Eukaryotic translation initiation factor 4E) resulting in enhanced eIF4E driven cap-dependent translation. In addition, the mTORC1 complex also activates ribosomal protein S6 kinases S6K1 and S6K2 that phosphorylates ribosomal S6 protein and eIF4B to regulate cap-independent protein biosynthesis. Negative regulators of insulin signalling:Intensity and duration of the signal play an important role in determining the specificity of the response. Uncontrolled signalling of insulin lead to severe perturbations in metabolism and often associated with tumorigenesis, hence, the ability to turn off the insulin signal in a rapid manner at different levels is critical. On the other hand, some of these inhibitory mechanisms can be altered in pathophysiological conditions to ameliorate insulin resistance.Phosphoprotein Phosphatases: Protein tyrosine phosphatases: Protein tyrosine phosphatases like protein-tyrosine phosphatase 1B (PTP1B) and leukocyte common antigen-related protein tyrosine phosphatase (LAR) have known to dephosphorylate the tyrosine residues on activated insulin receptor and IGF-1 receptor, as well as IRS proteins, thereby reducing their activity ADDIN EN.CITE <EndNote><Cite><Author>Goldstein</Author><Year>1998</Year><RecNum>250</RecNum><DisplayText>32</DisplayText><record><rec-number>250</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>250</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Goldstein, B. J.</author><author>Ahmad, F.</author><author>Ding, W.</author><author>Li, P. M.</author><author>Zhang, W. R.</author></authors></contributors><auth-address>Dorrance H. Hamilton Research Laboratories, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.</auth-address><titles><title>Regulation of the insulin signalling pathway by cellular protein-tyrosine phosphatases</title><secondary-title>Mol Cell Biochem</secondary-title><alt-title>Molecular and cellular biochemistry</alt-title></titles><periodical><full-title>Mol Cell Biochem</full-title><abbr-1>Molecular and cellular biochemistry</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biochem</full-title><abbr-1>Molecular and cellular biochemistry</abbr-1></alt-periodical><pages>91-9</pages><volume>182</volume><number>1-2</number><keywords><keyword>Animals</keyword><keyword>Humans</keyword><keyword>Insulin/*physiology</keyword><keyword>Protein Tyrosine Phosphatases/*physiology</keyword><keyword>Signal Transduction/drug effects/*physiology</keyword><keyword>Subcellular Fractions/enzymology/physiology</keyword></keywords><dates><year>1998</year><pub-dates><date>May</date></pub-dates></dates><isbn>0300-8177 (Print) 0300-8177 (Linking)</isbn><accession-num>9609118</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9609118</url></related-urls></urls></record></Cite></EndNote>32. LAR belongs to a subfamily of receptor PTPs. Till date the role of LAR in regulating insulin signalling under normal conditions in vivo is still unclear, however selective overexpression of LAR in the muscle of transgenic mice, to levels comparable to those reported in insulin-resistant human, resulted in whole-body insulin resistance with decreased IRS?2 phosphorylation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 33. PTP1B is predominantly localized near the endoplasmic reticulum 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 34 and preferentially dephosphorylates insulin receptor at Tyr1162 and Tyr1163 residues in vitro 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 35 and in cultured cells 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 36. It may also dephosphorylate IRS-1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 37, 38. Enhanced expression and activity of PTP1B are noted in obese and insulin-resistant human subjects as well as in some obese rodent models 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 39, 40. Further, PTP1B polymorphisms are associated with obesity and insulin resistance in humans 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 41, 42. The overexpression of PTP1B in muscle impaired insulin sensitivity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 43, consistently, mice lacking the PTP1B gene showed enhanced insulin sensitivity, increased insulin receptor phosphorylation in muscle and liver, and were resistant to high fat-diet-induced obesity and insulin resistance 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ADDIN EN.CITE.DATA 44. Moreover, antisense oligonucleotides that suppress PTP1B expression in mouse and rat animal models of insulin resistance can enhance insulin sensitivity and normalize blood glucose <EndNote><Cite><Author>Gum</Author><Year>2003</Year><RecNum>264</RecNum><DisplayText>[45-47]</DisplayText><record><rec-number>264</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">264</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gum, R. J.</author><author>Gaede, L. L.</author><author>Koterski, S. L.</author><author>Heindel, M.</author><author>Clampit, J. E.</author><author>Zinker, B. A.</author><author>Trevillyan, J. M.</author><author>Ulrich, R. G.</author><author>Jirousek, M. R.</author><author>Rondinone, C. M.</author></authors></contributors><auth-address>Metabolic Disease Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA. rebecca.gum@abbott.com</auth-address><titles><title>Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>21-8</pages><volume>52</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Diabetes Mellitus/genetics/metabolism/*physiopathology</keyword><keyword>Glycogen Synthase Kinase 3/metabolism</keyword><keyword>Glycogen Synthase Kinase 3 beta</keyword><keyword>Insulin/blood/pharmacology/*physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Liver/enzymology</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL/genetics</keyword><keyword>Muscle, Skeletal/enzymology</keyword><keyword>*Obesity</keyword><keyword>Oligonucleotides, Antisense/pharmacology</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/*antagonists &amp; inhibitors/genetics</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Serine/metabolism</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>12502489</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12502489</url></related-urls></urls></record></Cite><Cite><Author>Rondinone</Author><Year>2002</Year><RecNum>265</RecNum><record><rec-number>265</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">265</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rondinone, C. M.</author><author>Trevillyan, J. M.</author><author>Clampit, J.</author><author>Gum, R. J.</author><author>Berg, C.</author><author>Kroeger, P.</author><author>Frost, L.</author><author>Zinker, B. A.</author><author>Reilly, R.</author><author>Ulrich, R.</author><author>Butler, M.</author><author>Monia, B. P.</author><author>Jirousek, M. R.</author><author>Waring, J. F.</author></authors></contributors><auth-address>Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. cristina.rondinone@abbott.com</auth-address><titles><title>Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>2405-11</pages><volume>51</volume><number>8</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Adipose Tissue/drug effects/*physiopathology</keyword><keyword>Alternative Splicing</keyword><keyword>Animals</keyword><keyword>DNA Primers</keyword><keyword>Gene Expression Regulation/drug effects/*physiology</keyword><keyword>Genetic Variation</keyword><keyword>Homeostasis</keyword><keyword>Hyperglycemia/enzymology/genetics/physiopathology</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Intracellular Signaling Peptides and Proteins</keyword><keyword>Isoenzymes/genetics</keyword><keyword>Lipids/*biosynthesis</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>Oligodeoxyribonucleotides, Antisense/*pharmacology</keyword><keyword>Phosphatidylinositol 3-Kinases/genetics</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/genetics/*metabolism</keyword><keyword>Time Factors</keyword><keyword>Triglycerides/metabolism</keyword><keyword>Weight Loss/*physiology</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>12145151</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12145151</url></related-urls></urls></record></Cite><Cite><Author>Rondinone</Author><Year>2002</Year><RecNum>265</RecNum><record><rec-number>265</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">265</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rondinone, C. M.</author><author>Trevillyan, J. M.</author><author>Clampit, J.</author><author>Gum, R. J.</author><author>Berg, C.</author><author>Kroeger, P.</author><author>Frost, L.</author><author>Zinker, B. A.</author><author>Reilly, R.</author><author>Ulrich, R.</author><author>Butler, M.</author><author>Monia, B. P.</author><author>Jirousek, M. R.</author><author>Waring, J. F.</author></authors></contributors><auth-address>Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. cristina.rondinone@abbott.com</auth-address><titles><title>Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>2405-11</pages><volume>51</volume><number>8</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Adipose Tissue/drug effects/*physiopathology</keyword><keyword>Alternative Splicing</keyword><keyword>Animals</keyword><keyword>DNA Primers</keyword><keyword>Gene Expression Regulation/drug effects/*physiology</keyword><keyword>Genetic Variation</keyword><keyword>Homeostasis</keyword><keyword>Hyperglycemia/enzymology/genetics/physiopathology</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Intracellular Signaling Peptides and Proteins</keyword><keyword>Isoenzymes/genetics</keyword><keyword>Lipids/*biosynthesis</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>Oligodeoxyribonucleotides, Antisense/*pharmacology</keyword><keyword>Phosphatidylinositol 3-Kinases/genetics</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/genetics/*metabolism</keyword><keyword>Time Factors</keyword><keyword>Triglycerides/metabolism</keyword><keyword>Weight Loss/*physiology</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>12145151</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12145151</url></related-urls></urls></record></Cite><Cite><Author>Rondinone</Author><Year>2002</Year><RecNum>265</RecNum><record><rec-number>265</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">265</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rondinone, C. M.</author><author>Trevillyan, J. M.</author><author>Clampit, J.</author><author>Gum, R. J.</author><author>Berg, C.</author><author>Kroeger, P.</author><author>Frost, L.</author><author>Zinker, B. A.</author><author>Reilly, R.</author><author>Ulrich, R.</author><author>Butler, M.</author><author>Monia, B. P.</author><author>Jirousek, M. R.</author><author>Waring, J. F.</author></authors></contributors><auth-address>Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. cristina.rondinone@abbott.com</auth-address><titles><title>Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>2405-11</pages><volume>51</volume><number>8</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Adipose Tissue/drug effects/*physiopathology</keyword><keyword>Alternative Splicing</keyword><keyword>Animals</keyword><keyword>DNA Primers</keyword><keyword>Gene Expression Regulation/drug effects/*physiology</keyword><keyword>Genetic Variation</keyword><keyword>Homeostasis</keyword><keyword>Hyperglycemia/enzymology/genetics/physiopathology</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Intracellular Signaling Peptides and Proteins</keyword><keyword>Isoenzymes/genetics</keyword><keyword>Lipids/*biosynthesis</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>Oligodeoxyribonucleotides, Antisense/*pharmacology</keyword><keyword>Phosphatidylinositol 3-Kinases/genetics</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/genetics/*metabolism</keyword><keyword>Time Factors</keyword><keyword>Triglycerides/metabolism</keyword><keyword>Weight Loss/*physiology</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>12145151</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12145151</url></related-urls></urls></record></Cite><Cite><Author>Zinker</Author><Year>2002</Year><RecNum>267</RecNum><record><rec-number>267</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">267</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zinker, B. A.</author><author>Rondinone, C. M.</author><author>Trevillyan, J. M.</author><author>Gum, R. J.</author><author>Clampit, J. E.</author><author>Waring, J. F.</author><author>Xie, N.</author><author>Wilcox, D.</author><author>Jacobson, P.</author><author>Frost, L.</author><author>Kroeger, P. E.</author><author>Reilly, R. M.</author><author>Koterski, S.</author><author>Opgenorth, T. J.</author><author>Ulrich, R. G.</author><author>Crosby, S.</author><author>Butler, M.</author><author>Murray, S. F.</author><author>McKay, R. A.</author><author>Bhanot, S.</author><author>Monia, B. P.</author><author>Jirousek, M. R.</author></authors></contributors><auth-address>Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA. bradley.zinker@abbott.com</auth-address><titles><title>PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>11357-62</pages><volume>99</volume><number>17</number><keywords><keyword>Adipose Tissue/anatomy &amp; histology</keyword><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>Blood Glucose/drug effects/*metabolism</keyword><keyword>Crosses, Genetic</keyword><keyword>Diabetes Mellitus/*blood/drug therapy</keyword><keyword>Glucose Tolerance Test</keyword><keyword>Insulin/blood/pharmacology</keyword><keyword>Liver/anatomy &amp; histology</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>*Obesity</keyword><keyword>Oligodeoxyribonucleotides, Antisense/*pharmacology</keyword><keyword>Organ Size/drug effects</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/*genetics/metabolism</keyword><keyword>RNA, Complementary/genetics</keyword><keyword>Reference Values</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug 20</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>12169659</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12169659</url></related-urls></urls><custom2>123261</custom2><electronic-resource-num>10.1073/pnas.142298199</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Gum</Author><Year>2003</Year><RecNum>264</RecNum><DisplayText>[45-47]</DisplayText><record><rec-number>264</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">264</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gum, R. J.</author><author>Gaede, L. L.</author><author>Koterski, S. L.</author><author>Heindel, M.</author><author>Clampit, J. E.</author><author>Zinker, B. A.</author><author>Trevillyan, J. M.</author><author>Ulrich, R. G.</author><author>Jirousek, M. R.</author><author>Rondinone, C. M.</author></authors></contributors><auth-address>Metabolic Disease Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA. rebecca.gum@abbott.com</auth-address><titles><title>Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>21-8</pages><volume>52</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Diabetes Mellitus/genetics/metabolism/*physiopathology</keyword><keyword>Glycogen Synthase Kinase 3/metabolism</keyword><keyword>Glycogen Synthase Kinase 3 beta</keyword><keyword>Insulin/blood/pharmacology/*physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Liver/enzymology</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL/genetics</keyword><keyword>Muscle, Skeletal/enzymology</keyword><keyword>*Obesity</keyword><keyword>Oligonucleotides, Antisense/pharmacology</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/*antagonists &amp; inhibitors/genetics</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Serine/metabolism</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>12502489</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12502489</url></related-urls></urls></record></Cite><Cite><Author>Rondinone</Author><Year>2002</Year><RecNum>265</RecNum><record><rec-number>265</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">265</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rondinone, C. M.</author><author>Trevillyan, J. M.</author><author>Clampit, J.</author><author>Gum, R. J.</author><author>Berg, C.</author><author>Kroeger, P.</author><author>Frost, L.</author><author>Zinker, B. A.</author><author>Reilly, R.</author><author>Ulrich, R.</author><author>Butler, M.</author><author>Monia, B. P.</author><author>Jirousek, M. R.</author><author>Waring, J. F.</author></authors></contributors><auth-address>Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. cristina.rondinone@abbott.com</auth-address><titles><title>Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>2405-11</pages><volume>51</volume><number>8</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Adipose Tissue/drug effects/*physiopathology</keyword><keyword>Alternative Splicing</keyword><keyword>Animals</keyword><keyword>DNA Primers</keyword><keyword>Gene Expression Regulation/drug effects/*physiology</keyword><keyword>Genetic Variation</keyword><keyword>Homeostasis</keyword><keyword>Hyperglycemia/enzymology/genetics/physiopathology</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Intracellular Signaling Peptides and Proteins</keyword><keyword>Isoenzymes/genetics</keyword><keyword>Lipids/*biosynthesis</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>Oligodeoxyribonucleotides, Antisense/*pharmacology</keyword><keyword>Phosphatidylinositol 3-Kinases/genetics</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/genetics/*metabolism</keyword><keyword>Time Factors</keyword><keyword>Triglycerides/metabolism</keyword><keyword>Weight Loss/*physiology</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>12145151</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12145151</url></related-urls></urls></record></Cite><Cite><Author>Rondinone</Author><Year>2002</Year><RecNum>265</RecNum><record><rec-number>265</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">265</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rondinone, C. M.</author><author>Trevillyan, J. M.</author><author>Clampit, J.</author><author>Gum, R. J.</author><author>Berg, C.</author><author>Kroeger, P.</author><author>Frost, L.</author><author>Zinker, B. A.</author><author>Reilly, R.</author><author>Ulrich, R.</author><author>Butler, M.</author><author>Monia, B. P.</author><author>Jirousek, M. R.</author><author>Waring, J. F.</author></authors></contributors><auth-address>Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. cristina.rondinone@abbott.com</auth-address><titles><title>Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>2405-11</pages><volume>51</volume><number>8</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Adipose Tissue/drug effects/*physiopathology</keyword><keyword>Alternative Splicing</keyword><keyword>Animals</keyword><keyword>DNA Primers</keyword><keyword>Gene Expression Regulation/drug effects/*physiology</keyword><keyword>Genetic Variation</keyword><keyword>Homeostasis</keyword><keyword>Hyperglycemia/enzymology/genetics/physiopathology</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Intracellular Signaling Peptides and Proteins</keyword><keyword>Isoenzymes/genetics</keyword><keyword>Lipids/*biosynthesis</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>Oligodeoxyribonucleotides, Antisense/*pharmacology</keyword><keyword>Phosphatidylinositol 3-Kinases/genetics</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/genetics/*metabolism</keyword><keyword>Time Factors</keyword><keyword>Triglycerides/metabolism</keyword><keyword>Weight Loss/*physiology</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>12145151</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12145151</url></related-urls></urls></record></Cite><Cite><Author>Rondinone</Author><Year>2002</Year><RecNum>265</RecNum><record><rec-number>265</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">265</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rondinone, C. M.</author><author>Trevillyan, J. M.</author><author>Clampit, J.</author><author>Gum, R. J.</author><author>Berg, C.</author><author>Kroeger, P.</author><author>Frost, L.</author><author>Zinker, B. A.</author><author>Reilly, R.</author><author>Ulrich, R.</author><author>Butler, M.</author><author>Monia, B. P.</author><author>Jirousek, M. R.</author><author>Waring, J. F.</author></authors></contributors><auth-address>Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. cristina.rondinone@abbott.com</auth-address><titles><title>Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>2405-11</pages><volume>51</volume><number>8</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Adipose Tissue/drug effects/*physiopathology</keyword><keyword>Alternative Splicing</keyword><keyword>Animals</keyword><keyword>DNA Primers</keyword><keyword>Gene Expression Regulation/drug effects/*physiology</keyword><keyword>Genetic Variation</keyword><keyword>Homeostasis</keyword><keyword>Hyperglycemia/enzymology/genetics/physiopathology</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Intracellular Signaling Peptides and Proteins</keyword><keyword>Isoenzymes/genetics</keyword><keyword>Lipids/*biosynthesis</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>Oligodeoxyribonucleotides, Antisense/*pharmacology</keyword><keyword>Phosphatidylinositol 3-Kinases/genetics</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/genetics/*metabolism</keyword><keyword>Time Factors</keyword><keyword>Triglycerides/metabolism</keyword><keyword>Weight Loss/*physiology</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>12145151</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12145151</url></related-urls></urls></record></Cite><Cite><Author>Zinker</Author><Year>2002</Year><RecNum>267</RecNum><record><rec-number>267</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">267</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zinker, B. A.</author><author>Rondinone, C. M.</author><author>Trevillyan, J. M.</author><author>Gum, R. J.</author><author>Clampit, J. E.</author><author>Waring, J. F.</author><author>Xie, N.</author><author>Wilcox, D.</author><author>Jacobson, P.</author><author>Frost, L.</author><author>Kroeger, P. E.</author><author>Reilly, R. M.</author><author>Koterski, S.</author><author>Opgenorth, T. J.</author><author>Ulrich, R. G.</author><author>Crosby, S.</author><author>Butler, M.</author><author>Murray, S. F.</author><author>McKay, R. A.</author><author>Bhanot, S.</author><author>Monia, B. P.</author><author>Jirousek, M. R.</author></authors></contributors><auth-address>Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA. bradley.zinker@abbott.com</auth-address><titles><title>PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>11357-62</pages><volume>99</volume><number>17</number><keywords><keyword>Adipose Tissue/anatomy &amp; histology</keyword><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>Blood Glucose/drug effects/*metabolism</keyword><keyword>Crosses, Genetic</keyword><keyword>Diabetes Mellitus/*blood/drug therapy</keyword><keyword>Glucose Tolerance Test</keyword><keyword>Insulin/blood/pharmacology</keyword><keyword>Liver/anatomy &amp; histology</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>*Obesity</keyword><keyword>Oligodeoxyribonucleotides, Antisense/*pharmacology</keyword><keyword>Organ Size/drug effects</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatases/*genetics/metabolism</keyword><keyword>RNA, Complementary/genetics</keyword><keyword>Reference Values</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug 20</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>12169659</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12169659</url></related-urls></urls><custom2>123261</custom2><electronic-resource-num>10.1073/pnas.142298199</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 45-47.Interestingly, PTP1B also dephosphorylates JAK2 in the leptin signalling cascade resulting in leanness and protection from diet-induced obesity, a major cause of insulin resistance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 48, 49. Hence, to determine that the enhanced insulin sensitivity in PTP1B–/– mice are due to the direct effect on insulin receptor signalling not because of indirect effects resulting from leanness, homozygous PTP1B–/– mice were crossed with mice with a double heterozygous deficiency of insulin receptor and IRS-1 alleles (DHet). PTP1B deficiency reduces the severe hyperinsulinemia, insulin resistance, hyperglycemia, and ?-cell hypertrophy in DHet mice without affecting their body weight.TCPTP (T-cell protein tyrosine phosphatase) is another ubiquitously expressed tyrosine-specific phosphatase with two splice variants TC48, having a catalytic domain similar to PTP1B and TC45 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 36. Despite the high degree of sequence identity in the catalytic domain, PTP1B and TCPTP are non-redundant in nature and act in a temporally distinct manner to cooperatively regulate insulin receptor phosphorylation and signalling in the same cell. The insulin receptor is reported as a cellular substrate of TCPTP and activation and signalling through insulin receptor is enhanced in TCPTP ablated cells 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 50. TCPTP?/? immortalized mouse embryo fibroblasts (MEFs) showed an elevated or prolonged insulin receptor phosphorylation and PI3K/Akt signalling compared to TCPTP+/+ or TCPTP (TC45 or TC48) reconstituted MEFs. Insulin receptor ?-subunit phosphorylation at Y1162/Y1163 and Y972 both are elevated in PTP1B?/? MEFs, whereas Y972 phosphorylation was elevated and Y1162/Y1163 phosphorylation was sustained in TCPTP?/? MEFs, indicating that PTP1B and TCPTP differentially contribute to the regulation of insulin receptor phosphorylation and signalling 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ADDIN EN.CITE.DATA 36. Further, elevated Akt signalling was reported in human hepatoma HepG2 cells upon suppression of TCPTP protein levels and inactivation of reactive oxygen species produced in response to insulin has been shown by TC45, similar to PTP1B ADDIN EN.CITE <EndNote><Cite><Author>Meng</Author><Year>2004</Year><RecNum>272</RecNum><DisplayText>51</DisplayText><record><rec-number>272</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>272</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Meng, T. C.</author><author>Buckley, D. A.</author><author>Galic, S.</author><author>Tiganis, T.</author><author>Tonks, N. K.</author></authors></contributors><auth-address>Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.</auth-address><titles><title>Regulation of insulin signaling through reversible oxidation of the protein-tyrosine phosphatases TC45 and PTP1B</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>37716-25</pages><volume>279</volume><number>36</number><keywords><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>DNA Primers</keyword><keyword>Humans</keyword><keyword>Hydrogen Peroxide/pharmacology</keyword><keyword>Insulin/*metabolism</keyword><keyword>Oxidation-Reduction</keyword><keyword>Phosphorylation</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 1</keyword><keyword>Protein Tyrosine Phosphatase, Non-Receptor Type 2</keyword><keyword>Protein Tyrosine Phosphatases/*metabolism</keyword><keyword>Rats</keyword><keyword>*Signal Transduction/drug effects</keyword></keywords><dates><year>2004</year><pub-dates><date>Sep 3</date></pub-dates></dates><isbn>0021-9258 (Print) 0021-9258 (Linking)</isbn><accession-num>15192089</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15192089</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M404606200</electronic-resource-num></record></Cite></EndNote>51.Serine/threonine phosphatases:Phosphorylations at the Serine/threonine residues play an important in the metabolic actions of insulin. Serine/threonine phosphorylation of either the insulin receptor or IRS proteins acts to limit the insulin signalling while, it maintains the downstream proteins like serine/threonine kinases Akt and protein kinase C ? (PKC ?) in an active state 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 52. However, the phosphatases that catalyse corresponding dephosphorylation events have not been well identified. The role of serine-threonine phosphatases, such as protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), has not been fully elucidated. PP1-? is recently reported to dephosphorylate Akt substrate of 160 kDa (AS160) at Ser588 and Thr642 two key sites that control insulin-stimulated glucose transport in skeletal muscle 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 53. However, the most studied serine/threonine phosphatase controlling the action of insulin is Protein phosphatase 2A (PP2A). Accounting for about 80% of serine/threonine phosphatase activity in cells, it regulates the activity of some of the key mediators of insulin action such as Akt, PKC, S6K, ERK, and IKK 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 54. Inhibition of PP2A by okadaic acid activates glucose transport and GLUT4 translocation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 55. Indeed, PP2A is reported to directly dephosphorylate and inactivate both Akt and PKC ?, leading to the attenuation of glucose transport in 3T3-L1 adipocytes. Forced expression of small t-antigen that inhibits the association of PP2A with its substrate, in 3T3-L1 adipocytes enhanced the activity of Akt and protein kinase C ? (PKC ?) independent of wortmannin and upregulated basal as well as insulin-stimulated glucose uptake, which was inhibited upon expression of dominant negative Akt (DN-Akt) but not DN-PKC ? expression. Other serine/threonine phosphatases were also implicated in interfering with insulin action. Protein phosphatases 2B (PP2B), also known as calcineurin, has been shown to dephosphorylate Akt. Overexpression of constitutively active calcineurin triggered a significant decreased Akt phosphorylation, while overexpression of MCIP1.4, an endogenous inhibitor of calcineurin, had the opposite effect 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 56. In addition to the above, elevation of PP2C expression and activity is noted in TNF-?-induced insulin resistance rat skeletal muscle cells and insulin-resistant animal models 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 57. Further, two novel members of the PP2C family the PHLPP isozymes directly dephosphorylate both Akt and PKCs at their hydrophobic motifs and limit the action of insulin 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58, 59. (Detailed description of the inhibitory role of PHLPP in insulin action is described in the section 1.7.4).Lipid Phosphatases: Lipid phosphatases like PTEN and SHIP regulate insulin signalling by modulating PIP3 levels. PTEN (phosphatase and tensin homolog deleted on chromosome 10) was identified in a search for tumour suppressors on chromosome 10q23, a hot spot for loss of heterozygosity in many advanced-stage human tumours. It possesses both protein and lipid phosphatase activity. The lipid phosphatase activity attributes to its tumour suppressor role, while the protein phosphatase activity is intra-molecular and regulatory in nature ADDIN EN.CITE <EndNote><Cite><Author>Zhang</Author><Year>2012</Year><RecNum>276</RecNum><DisplayText>60</DisplayText><record><rec-number>276</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>276</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Zhang, X. C.</author><author>Piccini, A.</author><author>Myers, M. P.</author><author>Van Aelst, L.</author><author>Tonks, N. K.</author></authors></contributors><auth-address>Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.</auth-address><titles><title>Functional analysis of the protein phosphatase activity of PTEN</title><secondary-title>Biochem J</secondary-title><alt-title>The Biochemical journal</alt-title></titles><periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></periodical><alt-periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></alt-periodical><pages>457-64</pages><volume>444</volume><number>3</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Dendritic Spines/*enzymology/ultrastructure</keyword><keyword>Enzyme Activation/physiology</keyword><keyword>Hippocampus/*enzymology/ultrastructure</keyword><keyword>Molecular Sequence Data</keyword><keyword>Organ Culture Techniques</keyword><keyword>PTEN Phosphohydrolase/biosynthesis/genetics/*physiology</keyword><keyword>Phosphoprotein Phosphatases/biosynthesis/genetics/physiology</keyword><keyword>Rats</keyword></keywords><dates><year>2012</year><pub-dates><date>Jun 15</date></pub-dates></dates><isbn>1470-8728 (Electronic) 0264-6021 (Linking)</isbn><accession-num>22413754</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22413754</url></related-urls></urls><custom2>3365644</custom2><electronic-resource-num>10.1042/BJ20120098</electronic-resource-num></record></Cite></EndNote>60. PTEN functions in the cell as a phosphatidylinositol 3-phosphatase that dephosphorylates D3 phosphate of the inositol ring of PI(3,4,5)P3 (PIP3) to produce phosphatidylinositol 4,5-bisphosphate PI(4,5)P2 (PIP2) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 61. The link between the PI3K pathway and PTEN was paved by the finding that deletion of Pten in mouse embryonic fibroblasts (MEFs) activated AKT and elevated intracellular PIP3 levels 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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdGFtYm9saWM8L0F1dGhvcj48WWVhcj4xOTk4PC9ZZWFyPjxSZWNOdW0+Mjc4PC9SZWNOdW0+PERpc3BsYXlUZXh0Pls2Ml08L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+Mjc4PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0icGR0c2F2ZWQ3cHB3cjBlMHMycXZ6MnpmMHd4cngyeGQwYWF2Ij4yNzg8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlN0YW1ib2xpYywgVi48L2F1dGhvcj48YXV0aG9yPlN1enVraSwgQS48L2F1dGhvcj48YXV0aG9yPmRlIGxhIFBvbXBhLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+QnJvdGhlcnMsIEcuIE0uPC9hdXRob3I+PGF1dGhvcj5NaXJ0c29zLCBDLjwvYXV0aG9yPjxhdXRob3I+U2FzYWtpLCBULjwvYXV0aG9yPjxhdXRob3I+UnVsYW5kLCBKLjwvYXV0aG9yPjxhdXRob3I+UGVubmluZ2VyLCBKLiBNLjwvYXV0aG9yPjxhdXRob3I+U2lkZXJvdnNraSwgRC4gUC48L2F1dGhvcj48YXV0aG9yPk1haywgVC4gVy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5BbWdlbiBJbnN0aXR1dGUsIGFuZCBEZXBhcnRtZW50IG9mIE1lZGljYWwgQmlvcGh5c2ljcywgVW5pdmVyc2l0eSBvZiBUb3JvbnRvLCBPbnRhcmlvLCBDYW5hZGEuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+TmVnYXRpdmUgcmVndWxhdGlvbiBvZiBQS0IvQWt0LWRlcGVuZGVudCBjZWxsIHN1cnZpdmFsIGJ5IHRoZSB0dW1vciBzdXBwcmVzc29yIFBURU48L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Q2VsbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+Q2VsbDwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNlbGw8L2Z1bGwtdGl0bGU+PGFiYnItMT5DZWxsPC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5DZWxsPC9mdWxsLXRpdGxlPjxhYmJyLTE+Q2VsbDwvYWJici0xPjwvYWx0LXBlcmlvZGljYWw+PHBhZ2VzPjI5LTM5PC9wYWdlcz48dm9sdW1lPjk1PC92b2x1bWU+PG51bWJlcj4xPC9udW1iZXI+PGtleXdvcmRzPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtleXdvcmQ+KkFwb3B0b3Npczwva2V5d29yZD48a2V5d29yZD5DZWxsIERpdmlzaW9uPC9rZXl3b3JkPjxrZXl3b3JkPkNlbGwgU3Vydml2YWw8L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbHMsIEN1bHR1cmVkPC9rZXl3b3JkPjxrZXl3b3JkPkZlbWFsZTwva2V5d29yZD48a2V5d29yZD5GaWJyb2JsYXN0cy9jeXRvbG9neTwva2V5d29yZD48a2V5d29yZD4qR2VuZXMsIFR1bW9yIFN1cHByZXNzb3I8L2tleXdvcmQ+PGtleXdvcmQ+TWljZTwva2V5d29yZD48a2V5d29yZD5NdXRhZ2VuZXNpczwva2V5d29yZD48a2V5d29yZD5QVEVOIFBob3NwaG9oeWRyb2xhc2U8L2tleXdvcmQ+PGtleXdvcmQ+UGhvc3BoYXRpZHlsaW5vc2l0b2wgUGhvc3BoYXRlcy9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPipQaG9zcGhvcmljIE1vbm9lc3RlciBIeWRyb2xhc2VzPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RlaW4gVHlyb3NpbmUgUGhvc3BoYXRhc2VzL2dlbmV0aWNzLypwaHlzaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPipQcm90ZWluLVNlcmluZS1UaHJlb25pbmUgS2luYXNlczwva2V5d29yZD48a2V5d29yZD5Qcm90by1PbmNvZ2VuZSBQcm90ZWlucy9nZW5ldGljcy8qbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5Qcm90by1PbmNvZ2VuZSBQcm90ZWlucyBjLWFrdDwva2V5d29yZD48a2V5d29yZD5TdWJzdHJhdGUgU3BlY2lmaWNpdHk8L2tleXdvcmQ+PGtleXdvcmQ+KlR1bW9yIFN1cHByZXNzb3IgUHJvdGVpbnM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MTk5ODwveWVhcj48cHViLWRhdGVzPjxkYXRlPk9jdCAyPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDA5Mi04Njc0IChQcmludCkmI3hEOzAwOTItODY3NCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+OTc3ODI0NTwvYWNjZXNzaW9uLW51bT48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cDovL3d3dy5uY2JpLm5sbS5uaWguZ292L3B1Ym1lZC85Nzc4MjQ1PC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+ ADDIN EN.CITE.DATA 62. In addition, the reintroduction of PTEN in mutant PTEN tumour cell lines lowered Akt phosphorylation and cell death that could be rescued by myristoylated Akt, and inactivation of Pten in mice led to tumours with increased AKT phosphorylation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 63, 64. Organ-specific deletion of PTEN in muscle, adipose tissue, or liver in mice increased insulin sensitivity <EndNote><Cite><Author>Stiles</Author><Year>2004</Year><RecNum>282</RecNum><DisplayText>[65-67]</DisplayText><record><rec-number>282</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">282</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stiles, B.</author><author>Wang, Y.</author><author>Stahl, A.</author><author>Bassilian, S.</author><author>Lee, W. P.</author><author>Kim, Y. J.</author><author>Sherwin, R.</author><author>Devaskar, S.</author><author>Lesche, R.</author><author>Magnuson, M. A.</author><author>Wu, H.</author></authors></contributors><auth-address>Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA. bstiles@mednet.ucla.edu</auth-address><titles><title>Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>2082-7</pages><volume>101</volume><number>7</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Fasting/blood</keyword><keyword>Fatty Acids/biosynthesis/chemistry/secretion</keyword><keyword>Fatty Liver/complications/genetics/*metabolism/pathology</keyword><keyword>Gene Deletion</keyword><keyword>Gluconeogenesis</keyword><keyword>Glucose Tolerance Test</keyword><keyword>Glycogen/biosynthesis</keyword><keyword>Hepatocytes/pathology/secretion</keyword><keyword>Hepatomegaly/complications/genetics/metabolism/pathology</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Resistance</keyword><keyword>Liver/enzymology/*metabolism/pathology/secretion</keyword><keyword>Mice</keyword><keyword>Organ Specificity</keyword><keyword>RNA, Messenger/analysis/genetics</keyword></keywords><dates><year>2004</year><pub-dates><date>Feb 17</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>14769918</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14769918</url></related-urls></urls><custom2>357055</custom2><electronic-resource-num>10.1073/pnas.0308617100</electronic-resource-num></record></Cite><Cite><Author>Kurlawalla-Martinez</Author><Year>2005</Year><RecNum>283</RecNum><record><rec-number>283</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">283</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kurlawalla-Martinez, C.</author><author>Stiles, B.</author><author>Wang, Y.</author><author>Devaskar, S. U.</author><author>Kahn, B. B.</author><author>Wu, H.</author></authors></contributors><auth-address>Department of Pediatrics, Division of Neonatology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.</auth-address><titles><title>Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>2498-510</pages><volume>25</volume><number>6</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Adipose Tissue/enzymology/*metabolism</keyword><keyword>Animals</keyword><keyword>Cell Membrane/chemistry</keyword><keyword>Diabetes Mellitus, Experimental/*enzymology/genetics/metabolism</keyword><keyword>Fatty Acids/blood</keyword><keyword>Glucose Tolerance Test</keyword><keyword>Glucose Transporter Type 4</keyword><keyword>Hormones, Ectopic/blood/*metabolism</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Resistance/genetics/*physiology</keyword><keyword>Liver/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Monosaccharide Transport Proteins/analysis/metabolism</keyword><keyword>Muscle Cells/metabolism</keyword><keyword>Muscle Proteins/analysis/metabolism</keyword><keyword>PTEN Phosphohydrolase</keyword><keyword>Pancreas/cytology</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoric Monoester Hydrolases/genetics/*physiology</keyword><keyword>Protein Isoforms/metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword><keyword>Proto-Oncogene Proteins/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Resistin</keyword><keyword>Signal Transduction</keyword><keyword>Tumor Suppressor Proteins/genetics/*physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>15743841</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15743841</url></related-urls></urls><custom2>1061603</custom2><electronic-resource-num>10.1128/MCB.25.6.2498-2510.2005</electronic-resource-num></record></Cite><Cite><Author>Wijesekara</Author><Year>2005</Year><RecNum>284</RecNum><record><rec-number>284</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">284</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wijesekara, N.</author><author>Konrad, D.</author><author>Eweida, M.</author><author>Jefferies, C.</author><author>Liadis, N.</author><author>Giacca, A.</author><author>Crackower, M.</author><author>Suzuki, A.</author><author>Mak, T. W.</author><author>Kahn, C. R.</author><author>Klip, A.</author><author>Woo, M.</author></authors></contributors><auth-address>Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 2N9.</auth-address><titles><title>Muscle-specific Pten deletion protects against insulin resistance and diabetes</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>1135-45</pages><volume>25</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Deoxyglucose/metabolism</keyword><keyword>Diabetes Mellitus/genetics/*metabolism</keyword><keyword>Hyperinsulinism/genetics/metabolism</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/genetics/*physiology</keyword><keyword>Islets of Langerhans/*metabolism/pathology</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Muscle, Skeletal/*metabolism/pathology</keyword><keyword>PTEN Phosphohydrolase</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoric Monoester Hydrolases/genetics/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Tumor Suppressor Proteins/genetics/*metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>15657439</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15657439</url></related-urls></urls><custom2>544010</custom2><electronic-resource-num>10.1128/MCB.25.3.1135-1145.2005</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Stiles</Author><Year>2004</Year><RecNum>282</RecNum><DisplayText>[65-67]</DisplayText><record><rec-number>282</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">282</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stiles, B.</author><author>Wang, Y.</author><author>Stahl, A.</author><author>Bassilian, S.</author><author>Lee, W. P.</author><author>Kim, Y. J.</author><author>Sherwin, R.</author><author>Devaskar, S.</author><author>Lesche, R.</author><author>Magnuson, M. A.</author><author>Wu, H.</author></authors></contributors><auth-address>Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA. bstiles@mednet.ucla.edu</auth-address><titles><title>Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>2082-7</pages><volume>101</volume><number>7</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Fasting/blood</keyword><keyword>Fatty Acids/biosynthesis/chemistry/secretion</keyword><keyword>Fatty Liver/complications/genetics/*metabolism/pathology</keyword><keyword>Gene Deletion</keyword><keyword>Gluconeogenesis</keyword><keyword>Glucose Tolerance Test</keyword><keyword>Glycogen/biosynthesis</keyword><keyword>Hepatocytes/pathology/secretion</keyword><keyword>Hepatomegaly/complications/genetics/metabolism/pathology</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Resistance</keyword><keyword>Liver/enzymology/*metabolism/pathology/secretion</keyword><keyword>Mice</keyword><keyword>Organ Specificity</keyword><keyword>RNA, Messenger/analysis/genetics</keyword></keywords><dates><year>2004</year><pub-dates><date>Feb 17</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>14769918</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14769918</url></related-urls></urls><custom2>357055</custom2><electronic-resource-num>10.1073/pnas.0308617100</electronic-resource-num></record></Cite><Cite><Author>Kurlawalla-Martinez</Author><Year>2005</Year><RecNum>283</RecNum><record><rec-number>283</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">283</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kurlawalla-Martinez, C.</author><author>Stiles, B.</author><author>Wang, Y.</author><author>Devaskar, S. U.</author><author>Kahn, B. B.</author><author>Wu, H.</author></authors></contributors><auth-address>Department of Pediatrics, Division of Neonatology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.</auth-address><titles><title>Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>2498-510</pages><volume>25</volume><number>6</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Adipose Tissue/enzymology/*metabolism</keyword><keyword>Animals</keyword><keyword>Cell Membrane/chemistry</keyword><keyword>Diabetes Mellitus, Experimental/*enzymology/genetics/metabolism</keyword><keyword>Fatty Acids/blood</keyword><keyword>Glucose Tolerance Test</keyword><keyword>Glucose Transporter Type 4</keyword><keyword>Hormones, Ectopic/blood/*metabolism</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Resistance/genetics/*physiology</keyword><keyword>Liver/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Monosaccharide Transport Proteins/analysis/metabolism</keyword><keyword>Muscle Cells/metabolism</keyword><keyword>Muscle Proteins/analysis/metabolism</keyword><keyword>PTEN Phosphohydrolase</keyword><keyword>Pancreas/cytology</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoric Monoester Hydrolases/genetics/*physiology</keyword><keyword>Protein Isoforms/metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword><keyword>Proto-Oncogene Proteins/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Resistin</keyword><keyword>Signal Transduction</keyword><keyword>Tumor Suppressor Proteins/genetics/*physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>15743841</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15743841</url></related-urls></urls><custom2>1061603</custom2><electronic-resource-num>10.1128/MCB.25.6.2498-2510.2005</electronic-resource-num></record></Cite><Cite><Author>Wijesekara</Author><Year>2005</Year><RecNum>284</RecNum><record><rec-number>284</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">284</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wijesekara, N.</author><author>Konrad, D.</author><author>Eweida, M.</author><author>Jefferies, C.</author><author>Liadis, N.</author><author>Giacca, A.</author><author>Crackower, M.</author><author>Suzuki, A.</author><author>Mak, T. W.</author><author>Kahn, C. R.</author><author>Klip, A.</author><author>Woo, M.</author></authors></contributors><auth-address>Programme in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 2N9.</auth-address><titles><title>Muscle-specific Pten deletion protects against insulin resistance and diabetes</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>1135-45</pages><volume>25</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Deoxyglucose/metabolism</keyword><keyword>Diabetes Mellitus/genetics/*metabolism</keyword><keyword>Hyperinsulinism/genetics/metabolism</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/genetics/*physiology</keyword><keyword>Islets of Langerhans/*metabolism/pathology</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Muscle, Skeletal/*metabolism/pathology</keyword><keyword>PTEN Phosphohydrolase</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoric Monoester Hydrolases/genetics/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Tumor Suppressor Proteins/genetics/*metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>15657439</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15657439</url></related-urls></urls><custom2>544010</custom2><electronic-resource-num>10.1128/MCB.25.3.1135-1145.2005</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 65-67 and mice with whole-body PTEN haploinsufficiency, (as Pten deletion in mice is embryonic lethal), show improved glucose tolerance and increased insulin sensitivity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 68. In contrast, MEFs isolated from the PTEN-overexpressing mice (Ptentg mice) show reduced glucose/glutamine uptake, have increased mitochondrial oxidative phosphorylation, and are resistant to oncogenic transformation. Among SH2-domain-containing inositol phosphate 5-phosphatases isozymes, SHIP2 act as the negative regulator of insulin signalling which dephosphorylates PIP3 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ADDIN EN.CITE.DATA 69, as the expression of SHIP1 is limited to hematopoietic and lymphoid cells. Involvement of SHIP2 in impeding insulin action was anticipated as mutations in the SHIP2 gene, INPPL1, show genetic susceptibility of rats and human to type 2 diabetes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 70. Depletion of SHIP2 using antisense oligonucleotides improved the muscle insulin sensitivity in a diet-induced metabolic syndrome rat model 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 71. SHIP2 knockout (Inppl1?/?) mice show standard glucose and insulin levels with normal tolerance to insulin and glucose but are highly resistant to high fat-diet-induced obesity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 72. Conversely, SHIP2-overexpressing mice show reduced insulin-induced Akt activation in the liver, fat, and skeletal muscle 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 73 (Kagawa et al. 2008) and impaired neuroprotective effects of insulin in the brain 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 74.Adaptor Proteins:The cytoplasmic adaptor proteins like Grb10 and Grb14 bind to the insulin receptor and to a lesser extent IGF-1receptor to prevent access of substrates to the activated receptors 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 75. Loss of the Grb10 gene in mice augments growth, insulin signalling, and glucose tolerance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 76, 77, while its overexpression has opposing effects leading to insulin resistance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 78. Similar to GRB10, Grb14 knockout mice display increased glucose tolerance and insulin sensitivity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 79 and enhanced expression of Grb14 was noted in adipose tissue of insulin resistant animal models and type 2 diabetic (T2D) patients 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 80. The suppressor of cytokine signalling (SOCS) adaptor proteins, SOCS1 and SOCS3, also negatively regulate insulin signalling by either inhibiting the kinase activity of the insulin receptor or competing with the IRS proteins to bind to the receptor or by degrading the IRS proteins <EndNote><Cite><Author>Emanuelli</Author><Year>2000</Year><RecNum>299</RecNum><DisplayText>[81-83]</DisplayText><record><rec-number>299</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">299</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Emanuelli, B.</author><author>Peraldi, P.</author><author>Filloux, C.</author><author>Sawka-Verhelle, D.</author><author>Hilton, D.</author><author>Van Obberghen, E.</author></authors></contributors><auth-address>INSERM U145, IFR-50, Faculte de Medecine, 06107 Nice Cedex 2, France.</auth-address><titles><title>SOCS-3 is an insulin-induced negative regulator of insulin signaling</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>15985-91</pages><volume>275</volume><number>21</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/metabolism</keyword><keyword>Animals</keyword><keyword>COS Cells</keyword><keyword>DNA-Binding Proteins/metabolism</keyword><keyword>Gene Expression Regulation/*drug effects</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Mice</keyword><keyword>Microscopy, Fluorescence</keyword><keyword>*Milk Proteins</keyword><keyword>Mutation</keyword><keyword>Phosphorylation</keyword><keyword>Protein Binding</keyword><keyword>Proteins</keyword><keyword>RNA, Messenger/metabolism</keyword><keyword>Receptor, Insulin/genetics/metabolism</keyword><keyword>*Repressor Proteins</keyword><keyword>STAT5 Transcription Factor</keyword><keyword>*Signal Transduction</keyword><keyword>Suppressor of Cytokine Signaling 3 Protein</keyword><keyword>Suppressor of Cytokine Signaling Proteins</keyword><keyword>Trans-Activators/metabolism</keyword><keyword>*Transcription Factors</keyword><keyword>Transfection</keyword></keywords><dates><year>2000</year><pub-dates><date>May 26</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>10821852</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10821852</url></related-urls></urls></record></Cite><Cite><Author>Rui</Author><Year>2002</Year><RecNum>300</RecNum><record><rec-number>300</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">300</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rui, L.</author><author>Yuan, M.</author><author>Frantz, D.</author><author>Shoelson, S.</author><author>White, M. F.</author></authors></contributors><auth-address>Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.</auth-address><titles><title>SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>42394-8</pages><volume>277</volume><number>44</number><keywords><keyword>Animals</keyword><keyword>Carrier Proteins/*physiology</keyword><keyword>Elongin</keyword><keyword>Glucose/metabolism</keyword><keyword>Homeostasis</keyword><keyword>Humans</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>*Insulin Resistance</keyword><keyword>*Intracellular Signaling Peptides and Proteins</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Proteins/*physiology</keyword><keyword>*Repressor Proteins</keyword><keyword>Suppressor of Cytokine Signaling 1 Protein</keyword><keyword>Suppressor of Cytokine Signaling 3 Protein</keyword><keyword>Suppressor of Cytokine Signaling Proteins</keyword><keyword>Transcription Factors/physiology</keyword><keyword>Ubiquitin/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Nov 1</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>12228220</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12228220</url></related-urls></urls><electronic-resource-num>10.1074/jbc.C200444200</electronic-resource-num></record></Cite><Cite><Author>Ueki</Author><Year>2004</Year><RecNum>301</RecNum><record><rec-number>301</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">301</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ueki, K.</author><author>Kondo, T.</author><author>Kahn, C. R.</author></authors></contributors><auth-address>Research Division, Joslin Diabetes Center, and Departmentof Medicine, Harvard Medical School, Boston, MA 02215, USA.</auth-address><titles><title>Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>5434-46</pages><volume>24</volume><number>12</number><keywords><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>Carrier Proteins/genetics/*physiology</keyword><keyword>Cells, Cultured</keyword><keyword>DNA, Complementary/genetics</keyword><keyword>Endotoxemia/genetics/metabolism</keyword><keyword>Female</keyword><keyword>Gene Expression</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance/genetics/*physiology</keyword><keyword>Intracellular Signaling Peptides and Proteins</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Models, Biological</keyword><keyword>Phosphoproteins/chemistry/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Repressor Proteins/genetics/*physiology</keyword><keyword>Suppressor of Cytokine Signaling 1 Protein</keyword><keyword>Suppressor of Cytokine Signaling 3 Protein</keyword><keyword>Suppressor of Cytokine Signaling Proteins</keyword><keyword>Transcription Factors/genetics/*physiology</keyword><keyword>Tyrosine/chemistry</keyword><keyword>Up-Regulation</keyword></keywords><dates><year>2004</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>15169905</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15169905</url></related-urls></urls><custom2>419873</custom2><electronic-resource-num>10.1128/MCB.24.12.5434-5446.2004</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Emanuelli</Author><Year>2000</Year><RecNum>299</RecNum><DisplayText>[81-83]</DisplayText><record><rec-number>299</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">299</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Emanuelli, B.</author><author>Peraldi, P.</author><author>Filloux, C.</author><author>Sawka-Verhelle, D.</author><author>Hilton, D.</author><author>Van Obberghen, E.</author></authors></contributors><auth-address>INSERM U145, IFR-50, Faculte de Medecine, 06107 Nice Cedex 2, France.</auth-address><titles><title>SOCS-3 is an insulin-induced negative regulator of insulin signaling</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>15985-91</pages><volume>275</volume><number>21</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/metabolism</keyword><keyword>Animals</keyword><keyword>COS Cells</keyword><keyword>DNA-Binding Proteins/metabolism</keyword><keyword>Gene Expression Regulation/*drug effects</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Mice</keyword><keyword>Microscopy, Fluorescence</keyword><keyword>*Milk Proteins</keyword><keyword>Mutation</keyword><keyword>Phosphorylation</keyword><keyword>Protein Binding</keyword><keyword>Proteins</keyword><keyword>RNA, Messenger/metabolism</keyword><keyword>Receptor, Insulin/genetics/metabolism</keyword><keyword>*Repressor Proteins</keyword><keyword>STAT5 Transcription Factor</keyword><keyword>*Signal Transduction</keyword><keyword>Suppressor of Cytokine Signaling 3 Protein</keyword><keyword>Suppressor of Cytokine Signaling Proteins</keyword><keyword>Trans-Activators/metabolism</keyword><keyword>*Transcription Factors</keyword><keyword>Transfection</keyword></keywords><dates><year>2000</year><pub-dates><date>May 26</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>10821852</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10821852</url></related-urls></urls></record></Cite><Cite><Author>Rui</Author><Year>2002</Year><RecNum>300</RecNum><record><rec-number>300</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">300</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rui, L.</author><author>Yuan, M.</author><author>Frantz, D.</author><author>Shoelson, S.</author><author>White, M. F.</author></authors></contributors><auth-address>Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.</auth-address><titles><title>SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>42394-8</pages><volume>277</volume><number>44</number><keywords><keyword>Animals</keyword><keyword>Carrier Proteins/*physiology</keyword><keyword>Elongin</keyword><keyword>Glucose/metabolism</keyword><keyword>Homeostasis</keyword><keyword>Humans</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>*Insulin Resistance</keyword><keyword>*Intracellular Signaling Peptides and Proteins</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Proteins/*physiology</keyword><keyword>*Repressor Proteins</keyword><keyword>Suppressor of Cytokine Signaling 1 Protein</keyword><keyword>Suppressor of Cytokine Signaling 3 Protein</keyword><keyword>Suppressor of Cytokine Signaling Proteins</keyword><keyword>Transcription Factors/physiology</keyword><keyword>Ubiquitin/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Nov 1</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>12228220</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12228220</url></related-urls></urls><electronic-resource-num>10.1074/jbc.C200444200</electronic-resource-num></record></Cite><Cite><Author>Ueki</Author><Year>2004</Year><RecNum>301</RecNum><record><rec-number>301</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">301</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ueki, K.</author><author>Kondo, T.</author><author>Kahn, C. R.</author></authors></contributors><auth-address>Research Division, Joslin Diabetes Center, and Departmentof Medicine, Harvard Medical School, Boston, MA 02215, USA.</auth-address><titles><title>Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>5434-46</pages><volume>24</volume><number>12</number><keywords><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>Carrier Proteins/genetics/*physiology</keyword><keyword>Cells, Cultured</keyword><keyword>DNA, Complementary/genetics</keyword><keyword>Endotoxemia/genetics/metabolism</keyword><keyword>Female</keyword><keyword>Gene Expression</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance/genetics/*physiology</keyword><keyword>Intracellular Signaling Peptides and Proteins</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Models, Biological</keyword><keyword>Phosphoproteins/chemistry/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Repressor Proteins/genetics/*physiology</keyword><keyword>Suppressor of Cytokine Signaling 1 Protein</keyword><keyword>Suppressor of Cytokine Signaling 3 Protein</keyword><keyword>Suppressor of Cytokine Signaling Proteins</keyword><keyword>Transcription Factors/genetics/*physiology</keyword><keyword>Tyrosine/chemistry</keyword><keyword>Up-Regulation</keyword></keywords><dates><year>2004</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>15169905</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15169905</url></related-urls></urls><custom2>419873</custom2><electronic-resource-num>10.1128/MCB.24.12.5434-5446.2004</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 81-83. Elevated expression of both SOCS1 and SOCS3 are also noted in obese subjects.Tribbles homolog 3 (Trb3), a mammalian homolog of Drosophila tribbles, is a member of the family of pseudo-kinases that act as adaptor proteins and disrupts insulin signalling by binding directly to Akt and blocking activation of the kinase. Trb3 is an ER stress-inducible gene which is expressed in multiple tissues with strikingly different metabolic functions. In liver, elevated expression of Trb3 is detected upon fasting and in diabetic conditions. Ectopic expression of Trb3 in liver results in hyperglycemia, decreased glycogen content and impaired glucose tolerance 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ADDIN EN.CITE.DATA 84, while knockdown of Trb3 in mouse liver by RNAi improves glucose tolerance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 85. In Type 2 diabetic mice and humans the expression of Trb3 in pancreatic ?-cells is elevated which correlates with the inhibition of glucose-stimulated insulin secretion and impaired glucose homeostasis displayed by the pancreas specific Trb3 overexpressing mice 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 86. In skeletal muscle, elevated levels of Trb3 and other ER stress markers were detected in high-fat diet mice, obese and type 2 diabetic humans. While knockout of Trb3 protected mice from high fat diet-induced insulin resistance, overexpression of Trb3 in mouse myotubes and mouse tibialis anterior muscles significantly impaired insulin signalling, 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 87. However, in adipose tissue Trb3 functions independent of Akt and promotes lipolysis by triggering the ubiquitination and degradation of acetyl-CoA carboxylase. Transgenic mice expressing Trb3 in adipose tissue are protected from diet-induced obesity because of enhanced fatty acid oxidation and exhibited increased insulin sensitivity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 88.Another novel negative regulator of Akt activity is inositol pyrophosphate IP7, (diphosphoinositol pentakisphosphate 5-PP-1(1,2,3,4,6)IP5). Insulin and IGF-1 induce the expression of IP7 which inhibits Akt T308 phosphorylation and membrane translocation and subsequent activation of insulin signalling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 89. Loss of the enzyme IP6K1 involved in IP7 formation improved insulin responsiveness in mice.Inhibitory Ser/Thr phosphorylation:To propagate signalling, insulin requires tyrosine phosphorylation of insulin receptor/IGF-1receptor and IRS proteins, while serine and threonine phosphorylation turns the signalling off. The suppressed tyrosine kinase activity of insulin receptor is linked to its enhance Ser phosphorylation in insulin-resistant rodents and human <EndNote><Cite><Author>Karasik</Author><Year>1990</Year><RecNum>307</RecNum><DisplayText>[90-92]</DisplayText><record><rec-number>307</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">307</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Karasik, A.</author><author>Rothenberg, P. L.</author><author>Yamada, K.</author><author>White, M. F.</author><author>Kahn, C. R.</author></authors></contributors><auth-address>Joslin Diabetes Center, Department of Medicine, Brigham and Women&apos;s Hospital, Boston, Massachusetts.</auth-address><titles><title>Increased protein kinase C activity is linked to reduced insulin receptor autophosphorylation in liver of starved rats</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>10226-31</pages><volume>265</volume><number>18</number><keywords><keyword>Animals</keyword><keyword>Cell Membrane/enzymology</keyword><keyword>Cytosol/metabolism</keyword><keyword>Kinetics</keyword><keyword>Liver/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinase C/*metabolism</keyword><keyword>Protein Kinases/metabolism</keyword><keyword>Rats</keyword><keyword>Receptor, Insulin/isolation &amp; purification/*metabolism</keyword><keyword>Reference Values</keyword><keyword>Starvation</keyword></keywords><dates><year>1990</year><pub-dates><date>Jun 25</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>2354998</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/2354998</url></related-urls></urls></record></Cite><Cite><Author>Dunaif</Author><Year>1995</Year><RecNum>308</RecNum><record><rec-number>308</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">308</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dunaif, A.</author><author>Xia, J.</author><author>Book, C. B.</author><author>Schenker, E.</author><author>Tang, Z.</author></authors></contributors><auth-address>Department of Medicine, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA.</auth-address><titles><title>Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>801-10</pages><volume>96</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Cells, Cultured</keyword><keyword>Diabetes Mellitus, Type 2/etiology</keyword><keyword>Female</keyword><keyword>Fibroblasts/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/blood</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Muscle, Skeletal/*metabolism/pathology</keyword><keyword>Obesity/etiology</keyword><keyword>Peptides/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Phosphoserine/*metabolism</keyword><keyword>Polycystic Ovary Syndrome/complications/genetics/*physiopathology</keyword><keyword>*Protein Processing, Post-Translational</keyword><keyword>Protein-Serine-Threonine Kinases/genetics/*metabolism</keyword><keyword>Receptor, Insulin/*metabolism</keyword><keyword>Skin/pathology</keyword></keywords><dates><year>1995</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>7635975</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/7635975</url></related-urls></urls><custom2>185266</custom2><electronic-resource-num>10.1172/JCI118126</electronic-resource-num></record></Cite><Cite><Author>Zhou</Author><Year>1999</Year><RecNum>226</RecNum><record><rec-number>226</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">226</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhou, Q.</author><author>Dolan, P. L.</author><author>Dohm, G. L.</author></authors></contributors><auth-address>Department of Biochemistry, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA.</auth-address><titles><title>Dephosphorylation increases insulin-stimulated receptor kinase activity in skeletal muscle of obese Zucker rats</title><secondary-title>Mol Cell Biochem</secondary-title><alt-title>Molecular and cellular biochemistry</alt-title></titles><periodical><full-title>Mol Cell Biochem</full-title><abbr-1>Molecular and cellular biochemistry</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biochem</full-title><abbr-1>Molecular and cellular biochemistry</abbr-1></alt-periodical><pages>209-16</pages><volume>194</volume><number>1-2</number><keywords><keyword>Animals</keyword><keyword>Enzyme Activation</keyword><keyword>Glucose/metabolism</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Male</keyword><keyword>Muscle, Skeletal/*enzymology</keyword><keyword>Obesity/*enzymology</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Rats</keyword><keyword>Rats, Zucker</keyword><keyword>Receptor Protein-Tyrosine Kinases/*metabolism</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>1999</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0300-8177 (Print)&#xD;0300-8177 (Linking)</isbn><accession-num>10391142</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10391142</url></related-urls></urls></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Karasik</Author><Year>1990</Year><RecNum>307</RecNum><DisplayText>[90-92]</DisplayText><record><rec-number>307</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">307</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Karasik, A.</author><author>Rothenberg, P. L.</author><author>Yamada, K.</author><author>White, M. F.</author><author>Kahn, C. R.</author></authors></contributors><auth-address>Joslin Diabetes Center, Department of Medicine, Brigham and Women&apos;s Hospital, Boston, Massachusetts.</auth-address><titles><title>Increased protein kinase C activity is linked to reduced insulin receptor autophosphorylation in liver of starved rats</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>10226-31</pages><volume>265</volume><number>18</number><keywords><keyword>Animals</keyword><keyword>Cell Membrane/enzymology</keyword><keyword>Cytosol/metabolism</keyword><keyword>Kinetics</keyword><keyword>Liver/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinase C/*metabolism</keyword><keyword>Protein Kinases/metabolism</keyword><keyword>Rats</keyword><keyword>Receptor, Insulin/isolation &amp; purification/*metabolism</keyword><keyword>Reference Values</keyword><keyword>Starvation</keyword></keywords><dates><year>1990</year><pub-dates><date>Jun 25</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>2354998</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/2354998</url></related-urls></urls></record></Cite><Cite><Author>Dunaif</Author><Year>1995</Year><RecNum>308</RecNum><record><rec-number>308</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">308</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dunaif, A.</author><author>Xia, J.</author><author>Book, C. B.</author><author>Schenker, E.</author><author>Tang, Z.</author></authors></contributors><auth-address>Department of Medicine, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA.</auth-address><titles><title>Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>801-10</pages><volume>96</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Cells, Cultured</keyword><keyword>Diabetes Mellitus, Type 2/etiology</keyword><keyword>Female</keyword><keyword>Fibroblasts/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/blood</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Muscle, Skeletal/*metabolism/pathology</keyword><keyword>Obesity/etiology</keyword><keyword>Peptides/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Phosphoserine/*metabolism</keyword><keyword>Polycystic Ovary Syndrome/complications/genetics/*physiopathology</keyword><keyword>*Protein Processing, Post-Translational</keyword><keyword>Protein-Serine-Threonine Kinases/genetics/*metabolism</keyword><keyword>Receptor, Insulin/*metabolism</keyword><keyword>Skin/pathology</keyword></keywords><dates><year>1995</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>7635975</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/7635975</url></related-urls></urls><custom2>185266</custom2><electronic-resource-num>10.1172/JCI118126</electronic-resource-num></record></Cite><Cite><Author>Zhou</Author><Year>1999</Year><RecNum>226</RecNum><record><rec-number>226</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">226</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhou, Q.</author><author>Dolan, P. L.</author><author>Dohm, G. L.</author></authors></contributors><auth-address>Department of Biochemistry, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA.</auth-address><titles><title>Dephosphorylation increases insulin-stimulated receptor kinase activity in skeletal muscle of obese Zucker rats</title><secondary-title>Mol Cell Biochem</secondary-title><alt-title>Molecular and cellular biochemistry</alt-title></titles><periodical><full-title>Mol Cell Biochem</full-title><abbr-1>Molecular and cellular biochemistry</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biochem</full-title><abbr-1>Molecular and cellular biochemistry</abbr-1></alt-periodical><pages>209-16</pages><volume>194</volume><number>1-2</number><keywords><keyword>Animals</keyword><keyword>Enzyme Activation</keyword><keyword>Glucose/metabolism</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Male</keyword><keyword>Muscle, Skeletal/*enzymology</keyword><keyword>Obesity/*enzymology</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Rats</keyword><keyword>Rats, Zucker</keyword><keyword>Receptor Protein-Tyrosine Kinases/*metabolism</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>1999</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0300-8177 (Print)&#xD;0300-8177 (Linking)</isbn><accession-num>10391142</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10391142</url></related-urls></urls></record></Cite></EndNote> ADDIN EN.CITE.DATA 90-92. However, Ser/Thr phosphorylation of IRS proteins has a dual function. Although multiple inhibitory Ser phosphorylation sites have been detected on IRS1 protein ADDIN EN.CITE <EndNote><Cite><Author>Boura-Halfon</Author><Year>2009</Year><RecNum>310</RecNum><DisplayText>93</DisplayText><record><rec-number>310</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>310</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Boura-Halfon, S.</author><author>Zick, Y.</author></authors></contributors><auth-address>Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100 Israel.</auth-address><titles><title>Phosphorylation of IRS proteins, insulin action, and insulin resistance</title><secondary-title>Am J Physiol Endocrinol Metab</secondary-title><alt-title>American journal of physiology. Endocrinology and metabolism</alt-title></titles><periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></alt-periodical><pages>E581-91</pages><volume>296</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism/*physiology</keyword><keyword>Insulin Receptor Substrate Proteins/*metabolism/physiology</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Models, Biological</keyword><keyword>Phosphorylation/physiology</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism/physiology</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Signal Transduction/physiology</keyword></keywords><dates><year>2009</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0193-1849 (Print) 0193-1849 (Linking)</isbn><accession-num>18728222</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18728222</url></related-urls></urls><electronic-resource-num>10.1152/ajpendo.90437.2008</electronic-resource-num></record></Cite></EndNote>93, modifications at Ser-307 is widely studied 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 94. Phosphorylation at Ser-307 residues within the P-Tyr-binding (PTB) domain of IRS-1 by insulin-stimulated Akt protects IRS proteins from the rapid dephosphorylation and maintains IRS in Tyr phosphorylated active conformation 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ADDIN EN.CITE.DATA 95. In contrast, Ser/Thr phosphorylation on IRS-1/2 by kinases like JNK, IKK, conventional and novel PKCs, mTORC1/S6K and MAPK in response to cytokines, free fatty acids, hyperglycemia, mitochondrial dysfunction, and ER stress and insulin itself, play a predominant role in the pathophysiology of insulin resistance <EndNote><Cite><Author>De Fea</Author><Year>1997</Year><RecNum>312</RecNum><DisplayText>[96-100]</DisplayText><record><rec-number>312</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">312</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>De Fea, K.</author><author>Roth, R. A.</author></authors></contributors><auth-address>Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA.</auth-address><titles><title>Modulation of insulin receptor substrate-1 tyrosine phosphorylation and function by mitogen-activated protein kinase</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>31400-6</pages><volume>272</volume><number>50</number><keywords><keyword>Animals</keyword><keyword>CHO Cells</keyword><keyword>Calcium-Calmodulin-Dependent Protein Kinases/*metabolism</keyword><keyword>Cricetinae</keyword><keyword>Enzyme Activation</keyword><keyword>Humans</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Kidney/embryology</keyword><keyword>MAP Kinase Kinase 1</keyword><keyword>Mitogen-Activated Protein Kinase 1</keyword><keyword>Mitogen-Activated Protein Kinase 3</keyword><keyword>*Mitogen-Activated Protein Kinase Kinases</keyword><keyword>*Mitogen-Activated Protein Kinases</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword><keyword>Protein-Tyrosine Kinases/metabolism</keyword><keyword>Recombinant Proteins/metabolism</keyword><keyword>Serine/metabolism</keyword><keyword>Tetradecanoylphorbol Acetate/pharmacology</keyword><keyword>Tyrosine/*metabolism</keyword></keywords><dates><year>1997</year><pub-dates><date>Dec 12</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>9395471</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9395471</url></related-urls></urls></record></Cite><Cite><Author>Aguirre</Author><Year>2000</Year><RecNum>313</RecNum><record><rec-number>313</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">313</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Aguirre, V.</author><author>Uchida, T.</author><author>Yenush, L.</author><author>Davis, R.</author><author>White, M. F.</author></authors></contributors><auth-address>Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.</auth-address><titles><title>The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>9047-54</pages><volume>275</volume><number>12</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Anisomycin/pharmacology</keyword><keyword>CHO Cells</keyword><keyword>Cricetinae</keyword><keyword>Humans</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>JNK Mitogen-Activated Protein Kinases</keyword><keyword>Mice</keyword><keyword>Mitogen-Activated Protein Kinases/*metabolism</keyword><keyword>Molecular Sequence Data</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Binding</keyword><keyword>Receptor, Insulin/genetics/*metabolism</keyword><keyword>Recombinant Proteins/metabolism</keyword><keyword>Serine</keyword><keyword>Signal Transduction</keyword><keyword>Tumor Necrosis Factor-alpha/*pharmacology</keyword></keywords><dates><year>2000</year><pub-dates><date>Mar 24</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>10722755</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10722755</url></related-urls></urls></record></Cite><Cite><Author>Gao</Author><Year>2002</Year><RecNum>314</RecNum><record><rec-number>314</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">314</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gao, Z.</author><author>Hwang, D.</author><author>Bataille, F.</author><author>Lefevre, M.</author><author>York, D.</author><author>Quon, M. 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J.</author><author>Ye, J.</author></authors></contributors><auth-address>Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.</auth-address><titles><title>S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>35375-82</pages><volume>283</volume><number>51</number><keywords><keyword>Adipocytes/enzymology</keyword><keyword>Adipose Tissue/enzymology</keyword><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Gene Knockdown Techniques</keyword><keyword>Hepatocytes/enzymology</keyword><keyword>Humans</keyword><keyword>I-kappa B Kinase/genetics/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins/genetics/*metabolism</keyword><keyword>*Insulin Resistance/genetics</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>Phosphorylation/genetics</keyword><keyword>Point Mutation</keyword><keyword>Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism</keyword><keyword>*Signal Transduction/genetics</keyword><keyword>Tumor Necrosis Factor-alpha/genetics/*metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Dec 19</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>18952604</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18952604</url></related-urls></urls><custom2>2602883</custom2><electronic-resource-num>10.1074/jbc.M806480200</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 96-100. Inhibitors of the PI3K pathway suppressed the activity of the insulin-stimulated inhibitory kinases indicating the role of downstream effectors of PI3K as negative regulators of IRS protein function 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 95, 101. The potential candidate for the negative feedback loop in insulin signalling is the mTORC1-S6K pathway which enhances phosphorylation of Ser residues at the C-terminus of IRS-1 leading to inhibition of insulin-stimulated Tyr phosphorylation of IRS-1 and its ability to bind to PI3K <EndNote><Cite><Author>Li</Author><Year>1999</Year><RecNum>398</RecNum><DisplayText>[102-104]</DisplayText><record><rec-number>398</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">398</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, J.</author><author>DeFea, K.</author><author>Roth, R. A.</author></authors></contributors><auth-address>Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA.</auth-address><titles><title>Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>9351-6</pages><volume>274</volume><number>14</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/drug effects/metabolism</keyword><keyword>Animals</keyword><keyword>Endothelin-1/*pharmacology</keyword><keyword>Flavonoids/pharmacology</keyword><keyword>Insulin/pharmacology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Mice</keyword><keyword>Phosphatidylinositol 3-Kinases/*metabolism</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Platelet-Derived Growth Factor/pharmacology</keyword><keyword>Protein-Serine-Threonine Kinases/*metabolism</keyword><keyword>*Proto-Oncogene Proteins</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Sirolimus/pharmacology</keyword><keyword>Tyrosine/*metabolism</keyword></keywords><dates><year>1999</year><pub-dates><date>Apr 2</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>10092613</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10092613</url></related-urls></urls></record></Cite><Cite><Author>Ozes</Author><Year>2001</Year><RecNum>399</RecNum><record><rec-number>399</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">399</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozes, O. N.</author><author>Akca, H.</author><author>Mayo, L. D.</author><author>Gustin, J. A.</author><author>Maehama, T.</author><author>Dixon, J. E.</author><author>Donner, D. B.</author></authors></contributors><auth-address>Department of Microbiology and Immunology, Indiana University School of Medicine and the Walther Oncology Center, Indianapolis, IN 46202, USA.</auth-address><titles><title>A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>4640-5</pages><volume>98</volume><number>8</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Cell Line</keyword><keyword>Chromatography, Liquid</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance</keyword><keyword>Molecular Sequence Data</keyword><keyword>PTEN Phosphohydrolase</keyword><keyword>Phosphatidylinositol 3-Kinases/*metabolism</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Phosphoric Monoester Hydrolases/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Phosphotransferases (Alcohol Group Acceptor)/*metabolism</keyword><keyword>*Protein Kinases</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>*Signal Transduction</keyword><keyword>Spectrometry, Mass, Electrospray Ionization</keyword><keyword>TOR Serine-Threonine Kinases</keyword><keyword>Tumor Necrosis Factor-alpha/*antagonists &amp; inhibitors</keyword><keyword>*Tumor Suppressor Proteins</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr 10</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>11287630</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11287630</url></related-urls></urls><custom2>31887</custom2><electronic-resource-num>10.1073/pnas.051042298</electronic-resource-num></record></Cite><Cite><Author>Tremblay</Author><Year>2001</Year><RecNum>400</RecNum><record><rec-number>400</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">400</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tremblay, F.</author><author>Marette, A.</author></authors></contributors><auth-address>Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center, Ste-Foy, Quebec G1V 4G2, Canada.</auth-address><titles><title>Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>38052-60</pages><volume>276</volume><number>41</number><keywords><keyword>Amino Acids/*metabolism</keyword><keyword>Biological Transport</keyword><keyword>Cell Line</keyword><keyword>Enzyme Activation</keyword><keyword>Feedback</keyword><keyword>Glucose/metabolism</keyword><keyword>Hydrolysis</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>*Insulin Resistance</keyword><keyword>Muscle, Skeletal/cytology/*metabolism</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinases/*metabolism</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Ribosomal Protein S6 Kinases/*metabolism</keyword><keyword>*Signal Transduction</keyword><keyword>TOR Serine-Threonine Kinases</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Oct 12</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>11498541</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11498541</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M106703200</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Li</Author><Year>1999</Year><RecNum>398</RecNum><DisplayText>[102-104]</DisplayText><record><rec-number>398</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">398</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, J.</author><author>DeFea, K.</author><author>Roth, R. A.</author></authors></contributors><auth-address>Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA.</auth-address><titles><title>Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>9351-6</pages><volume>274</volume><number>14</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/drug effects/metabolism</keyword><keyword>Animals</keyword><keyword>Endothelin-1/*pharmacology</keyword><keyword>Flavonoids/pharmacology</keyword><keyword>Insulin/pharmacology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Mice</keyword><keyword>Phosphatidylinositol 3-Kinases/*metabolism</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Platelet-Derived Growth Factor/pharmacology</keyword><keyword>Protein-Serine-Threonine Kinases/*metabolism</keyword><keyword>*Proto-Oncogene Proteins</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Sirolimus/pharmacology</keyword><keyword>Tyrosine/*metabolism</keyword></keywords><dates><year>1999</year><pub-dates><date>Apr 2</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>10092613</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10092613</url></related-urls></urls></record></Cite><Cite><Author>Ozes</Author><Year>2001</Year><RecNum>399</RecNum><record><rec-number>399</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">399</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozes, O. N.</author><author>Akca, H.</author><author>Mayo, L. D.</author><author>Gustin, J. A.</author><author>Maehama, T.</author><author>Dixon, J. E.</author><author>Donner, D. B.</author></authors></contributors><auth-address>Department of Microbiology and Immunology, Indiana University School of Medicine and the Walther Oncology Center, Indianapolis, IN 46202, USA.</auth-address><titles><title>A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>4640-5</pages><volume>98</volume><number>8</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Cell Line</keyword><keyword>Chromatography, Liquid</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance</keyword><keyword>Molecular Sequence Data</keyword><keyword>PTEN Phosphohydrolase</keyword><keyword>Phosphatidylinositol 3-Kinases/*metabolism</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Phosphoric Monoester Hydrolases/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Phosphotransferases (Alcohol Group Acceptor)/*metabolism</keyword><keyword>*Protein Kinases</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>*Signal Transduction</keyword><keyword>Spectrometry, Mass, Electrospray Ionization</keyword><keyword>TOR Serine-Threonine Kinases</keyword><keyword>Tumor Necrosis Factor-alpha/*antagonists &amp; inhibitors</keyword><keyword>*Tumor Suppressor Proteins</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr 10</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>11287630</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11287630</url></related-urls></urls><custom2>31887</custom2><electronic-resource-num>10.1073/pnas.051042298</electronic-resource-num></record></Cite><Cite><Author>Tremblay</Author><Year>2001</Year><RecNum>400</RecNum><record><rec-number>400</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">400</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tremblay, F.</author><author>Marette, A.</author></authors></contributors><auth-address>Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center, Ste-Foy, Quebec G1V 4G2, Canada.</auth-address><titles><title>Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>38052-60</pages><volume>276</volume><number>41</number><keywords><keyword>Amino Acids/*metabolism</keyword><keyword>Biological Transport</keyword><keyword>Cell Line</keyword><keyword>Enzyme Activation</keyword><keyword>Feedback</keyword><keyword>Glucose/metabolism</keyword><keyword>Hydrolysis</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>*Insulin Resistance</keyword><keyword>Muscle, Skeletal/cytology/*metabolism</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinases/*metabolism</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Ribosomal Protein S6 Kinases/*metabolism</keyword><keyword>*Signal Transduction</keyword><keyword>TOR Serine-Threonine Kinases</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Oct 12</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>11498541</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11498541</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M106703200</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 102-104. Hence, S6K null mice displayed enhanced insulin sensitivity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 105, while constitutive activation of S6K in TSC-2 knockout fibroblasts resulted in hyper phosphorylation and degradation of IRS-1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 106. In addition, mTORC1 also phosphorylates and stabilizes Grb10, leading to feedback inhibition of insulin signalling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 107. Further, classical (?, ?, ?) as well as novel PKC members (?, ?, ?) induces multiple serine phosphorylations of IRS proteins and insulin receptor and thereby impair insulin signalling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 108-110. Thus, deletion of any member of the novel PKC family prevents the development of insulin resistance in skeletal muscle and liver by decreasing IRS-1 Ser307 phosphorylation <EndNote><Cite><Author>Kim</Author><Year>2004</Year><RecNum>323</RecNum><DisplayText>[111-113]</DisplayText><record><rec-number>323</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">323</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kim, J. K.</author><author>Fillmore, J. J.</author><author>Sunshine, M. J.</author><author>Albrecht, B.</author><author>Higashimori, T.</author><author>Kim, D. W.</author><author>Liu, Z. X.</author><author>Soos, T. J.</author><author>Cline, G. W.</author><author>O&apos;Brien, W. R.</author><author>Littman, D. R.</author><author>Shulman, G. I.</author></authors></contributors><auth-address>Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA. jason.k.kim@yale.edu</auth-address><titles><title>PKC-theta knockout mice are protected from fat-induced insulin resistance</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>823-7</pages><volume>114</volume><number>6</number><keywords><keyword>Adipose Tissue/*physiology</keyword><keyword>Animals</keyword><keyword>Blood Glucose/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/therapy</keyword><keyword>Fatty Acids, Nonesterified/blood</keyword><keyword>Infusions, Intravenous</keyword><keyword>Insulin/blood/physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance/*genetics</keyword><keyword>Isoenzymes/*deficiency/*genetics/therapeutic use</keyword><keyword>Lipids/administration &amp; dosage/pharmacology</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Muscle, Skeletal/physiology</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinase C/*deficiency/*genetics/therapeutic use</keyword><keyword>Protein Kinase C-theta</keyword><keyword>Signal Transduction/genetics/physiology</keyword></keywords><dates><year>2004</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>15372106</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15372106</url></related-urls></urls><custom2>516267</custom2><electronic-resource-num>10.1172/JCI22230</electronic-resource-num></record></Cite><Cite><Author>Samuel</Author><Year>2007</Year><RecNum>324</RecNum><record><rec-number>324</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">324</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Samuel, V. T.</author><author>Liu, Z. X.</author><author>Wang, A.</author><author>Beddow, S. A.</author><author>Geisler, J. G.</author><author>Kahn, M.</author><author>Zhang, X. M.</author><author>Monia, B. P.</author><author>Bhanot, S.</author><author>Shulman, G. I.</author></authors></contributors><auth-address>Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.</auth-address><titles><title>Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>739-45</pages><volume>117</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Fatty Liver/*enzymology</keyword><keyword>Insulin/blood/*metabolism</keyword><keyword>*Insulin Resistance/genetics</keyword><keyword>Lipid Metabolism</keyword><keyword>Male</keyword><keyword>Oligonucleotides, Antisense/pharmacology</keyword><keyword>Protein Kinase C-epsilon/antagonists &amp; inhibitors/genetics/*physiology</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Receptor, Insulin/agonists</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2007</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>17318260</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17318260</url></related-urls></urls><custom2>1797607</custom2><electronic-resource-num>10.1172/JCI30400</electronic-resource-num></record></Cite><Cite><Author>Bezy</Author><Year>2011</Year><RecNum>325</RecNum><record><rec-number>325</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">325</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bezy, O.</author><author>Tran, T. T.</author><author>Pihlajamaki, J.</author><author>Suzuki, R.</author><author>Emanuelli, B.</author><author>Winnay, J.</author><author>Mori, M. A.</author><author>Haas, J.</author><author>Biddinger, S. B.</author><author>Leitges, M.</author><author>Goldfine, A. B.</author><author>Patti, M. E.</author><author>King, G. L.</author><author>Kahn, C. R.</author></authors></contributors><auth-address>Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA.</auth-address><titles><title>PKCdelta regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>2504-17</pages><volume>121</volume><number>6</number><keywords><keyword>Aging/metabolism</keyword><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Diabetes Mellitus, Experimental/enzymology/genetics/therapy</keyword><keyword>Dietary Fats/toxicity</keyword><keyword>Enzyme Induction/drug effects</keyword><keyword>Fasting/blood</keyword><keyword>Fatty Liver/*enzymology/etiology</keyword><keyword>Female</keyword><keyword>Gluconeogenesis/drug effects/genetics</keyword><keyword>Glucose Intolerance/enzymology/genetics</keyword><keyword>Humans</keyword><keyword>Insulin/pharmacology</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Lipogenesis/drug effects/genetics</keyword><keyword>Liver/*enzymology</keyword><keyword>Male</keyword><keyword>Metabolic Syndrome/enzymology/prevention &amp; control</keyword><keyword>Mice</keyword><keyword>Mice, 129 Strain</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Knockout</keyword><keyword>Obesity/complications/*enzymology</keyword><keyword>Protein Kinase C-delta/biosynthesis/deficiency/genetics/*physiology</keyword><keyword>Species Specificity</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>2011</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1558-8238 (Electronic)&#xD;0021-9738 (Linking)</isbn><accession-num>21576825</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21576825</url></related-urls></urls><custom2>3104767</custom2><electronic-resource-num>10.1172/JCI46045</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Kim</Author><Year>2004</Year><RecNum>323</RecNum><DisplayText>[111-113]</DisplayText><record><rec-number>323</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">323</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kim, J. K.</author><author>Fillmore, J. J.</author><author>Sunshine, M. J.</author><author>Albrecht, B.</author><author>Higashimori, T.</author><author>Kim, D. W.</author><author>Liu, Z. X.</author><author>Soos, T. J.</author><author>Cline, G. W.</author><author>O&apos;Brien, W. R.</author><author>Littman, D. R.</author><author>Shulman, G. I.</author></authors></contributors><auth-address>Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA. jason.k.kim@yale.edu</auth-address><titles><title>PKC-theta knockout mice are protected from fat-induced insulin resistance</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>823-7</pages><volume>114</volume><number>6</number><keywords><keyword>Adipose Tissue/*physiology</keyword><keyword>Animals</keyword><keyword>Blood Glucose/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/therapy</keyword><keyword>Fatty Acids, Nonesterified/blood</keyword><keyword>Infusions, Intravenous</keyword><keyword>Insulin/blood/physiology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance/*genetics</keyword><keyword>Isoenzymes/*deficiency/*genetics/therapeutic use</keyword><keyword>Lipids/administration &amp; dosage/pharmacology</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Muscle, Skeletal/physiology</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinase C/*deficiency/*genetics/therapeutic use</keyword><keyword>Protein Kinase C-theta</keyword><keyword>Signal Transduction/genetics/physiology</keyword></keywords><dates><year>2004</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>15372106</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15372106</url></related-urls></urls><custom2>516267</custom2><electronic-resource-num>10.1172/JCI22230</electronic-resource-num></record></Cite><Cite><Author>Samuel</Author><Year>2007</Year><RecNum>324</RecNum><record><rec-number>324</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">324</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Samuel, V. T.</author><author>Liu, Z. X.</author><author>Wang, A.</author><author>Beddow, S. A.</author><author>Geisler, J. G.</author><author>Kahn, M.</author><author>Zhang, X. M.</author><author>Monia, B. P.</author><author>Bhanot, S.</author><author>Shulman, G. I.</author></authors></contributors><auth-address>Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.</auth-address><titles><title>Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>739-45</pages><volume>117</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Fatty Liver/*enzymology</keyword><keyword>Insulin/blood/*metabolism</keyword><keyword>*Insulin Resistance/genetics</keyword><keyword>Lipid Metabolism</keyword><keyword>Male</keyword><keyword>Oligonucleotides, Antisense/pharmacology</keyword><keyword>Protein Kinase C-epsilon/antagonists &amp; inhibitors/genetics/*physiology</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Receptor, Insulin/agonists</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2007</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>17318260</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17318260</url></related-urls></urls><custom2>1797607</custom2><electronic-resource-num>10.1172/JCI30400</electronic-resource-num></record></Cite><Cite><Author>Bezy</Author><Year>2011</Year><RecNum>325</RecNum><record><rec-number>325</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">325</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bezy, O.</author><author>Tran, T. T.</author><author>Pihlajamaki, J.</author><author>Suzuki, R.</author><author>Emanuelli, B.</author><author>Winnay, J.</author><author>Mori, M. A.</author><author>Haas, J.</author><author>Biddinger, S. B.</author><author>Leitges, M.</author><author>Goldfine, A. B.</author><author>Patti, M. E.</author><author>King, G. L.</author><author>Kahn, C. R.</author></authors></contributors><auth-address>Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA.</auth-address><titles><title>PKCdelta regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>2504-17</pages><volume>121</volume><number>6</number><keywords><keyword>Aging/metabolism</keyword><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Diabetes Mellitus, Experimental/enzymology/genetics/therapy</keyword><keyword>Dietary Fats/toxicity</keyword><keyword>Enzyme Induction/drug effects</keyword><keyword>Fasting/blood</keyword><keyword>Fatty Liver/*enzymology/etiology</keyword><keyword>Female</keyword><keyword>Gluconeogenesis/drug effects/genetics</keyword><keyword>Glucose Intolerance/enzymology/genetics</keyword><keyword>Humans</keyword><keyword>Insulin/pharmacology</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Lipogenesis/drug effects/genetics</keyword><keyword>Liver/*enzymology</keyword><keyword>Male</keyword><keyword>Metabolic Syndrome/enzymology/prevention &amp; control</keyword><keyword>Mice</keyword><keyword>Mice, 129 Strain</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Knockout</keyword><keyword>Obesity/complications/*enzymology</keyword><keyword>Protein Kinase C-delta/biosynthesis/deficiency/genetics/*physiology</keyword><keyword>Species Specificity</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>2011</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1558-8238 (Electronic)&#xD;0021-9738 (Linking)</isbn><accession-num>21576825</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21576825</url></related-urls></urls><custom2>3104767</custom2><electronic-resource-num>10.1172/JCI46045</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 111-113. Atypical PKC-? also inhibits insulin signalling by inducing serine phosphorylation of IRS-1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 114 and Thr34 phosphorylation of Akt, thereby constraining its association with the plasma membrane 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ADDIN EN.CITE.DATA 115. In brief, insulin signalling controls glucose and lipid metabolism, predominantly via action on insulin-sensitive tissues like liver, skeletal muscle, and adipose tissue. Precise regulation of this signalling cascade is important for apt adaption of energy homeostasis. Insulin signalling contains several critical nodes, controlled both positively and negatively, to ascertain appropriate signal duration as well as intensity (Figure 1.3). Several nodes in the insulin signalling cascade are negatively controlled by the action of phosphatases and/or inhibitory proteins. Perturbations in these signalling pathways can lead to insulin resistance. Based on numerous studies, supported by cell-based, animal models as well as clinical observations, the causes of insulin resistance are numerous and the mechanisms are multifactorial. Below, we discuss different drivers which lead to deregulation of gene and inhibitory protein modifications resulting in impaired insulin action. Insulin resistance and its drivers:Insulin resistance (IR) is the hallmark feature of most patients with Type 2 diabetes mellitus (T2D) and is attributed to the sub-optimal response of the body to insulin. Clinically, the term “insulin resistance” implies to elevated levels of insulin (hyperinsulinemia) which is required to maintain normoglycemia. At the molecular level of the cell, IR is defined as the inadequate transmission of insulin signalling from the insulin receptor to the downstream substrates involved in several metabolic and mitogenic cellular functions ADDIN EN.CITE <EndNote><Cite><Author>Ginsberg</Author><Year>2000</Year><RecNum>211</RecNum><DisplayText>116</DisplayText><record><rec-number>211</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>211</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ginsberg, H. N.</author></authors></contributors><auth-address>Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA. [email protected]</auth-address><titles><title>Insulin resistance and cardiovascular disease</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>453-8</pages><volume>106</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Arteriosclerosis/etiology/physiopathology</keyword><keyword>Blood Coagulation/physiology</keyword><keyword>Cardiovascular Diseases/*etiology/physiopathology</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Humans</keyword><keyword>Hyperlipidemias/etiology/physiopathology</keyword><keyword>Hypertension/etiology/physiopathology</keyword><keyword>Insulin/blood</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Lipoproteins, VLDL/metabolism</keyword><keyword>Models, Biological</keyword><keyword>Triglycerides/metabolism</keyword></keywords><dates><year>2000</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0021-9738 (Print) 0021-9738 (Linking)</isbn><accession-num>10953019</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10953019</url></related-urls></urls><custom2>380256</custom2><electronic-resource-num>10.1172/JCI10762</electronic-resource-num></record></Cite></EndNote>116. In fact, the pathogenesis of type 2 diabetes involves abnormalities in both insulin action as well as secretion ADDIN EN.CITE <EndNote><Cite><Author>Saltiel</Author><Year>2001</Year><RecNum>212</RecNum><DisplayText>117</DisplayText><record><rec-number>212</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>212</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Saltiel, A. R.</author></authors></contributors><auth-address>Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.</auth-address><titles><title>New perspectives into the molecular pathogenesis and treatment of type 2 diabetes</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>517-29</pages><volume>104</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Blood Glucose/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/*etiology/genetics/*metabolism/physiopathology/*therapy</keyword><keyword>Glycogen/biosynthesis</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance</keyword><keyword>Islets of Langerhans/metabolism</keyword><keyword>Models, Biological</keyword><keyword>Obesity</keyword><keyword>Protein-Tyrosine Kinases/metabolism</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Receptors, Cytoplasmic and Nuclear/metabolism</keyword><keyword>Signal Transduction</keyword><keyword>Transcription Factors/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Feb 23</date></pub-dates></dates><isbn>0092-8674 (Print) 0092-8674 (Linking)</isbn><accession-num>11239409</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11239409</url></related-urls></urls></record></Cite></EndNote>117. Based on numerous clinical, pre-clinical and cellular studies, several genetic and environmental factors are directly linked to the pathogenesis of IR (Figure 1.4). Some of these factors are discussed in brief below. 1.4.1.Genetic causes of insulin resistance:A genetic point of view of IR is thought of due to the inheritance of a number of mutations in a variety of genes. Three complementary approaches have been applied in the search for mutations: mutational analysis of candidate genes; linkage analysis of candidate genes or chromosomal regions for IR in familial T2D; and random genome mapping with quantitative trait loci (QTL) analysis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 118, 119. During the last decade, genome-wide association studies (GWAS) have identified approximately 88 loci associated with risk of developing T2D, most of which are sorted to be associated with ?-cell function and insulin secretion 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 119, 120. Few of the mutations /genetic alterations which are studied in detail are listed here.Nonsense or missense mutations in the extracellular ligand-binding domain or intracellular tyrosine kinase domain of the insulin receptor that leads to severely reduced insulin binding, altered kinetics of insulin binding, or reduced tyrosine kinase activity, or promoter defects leading to reduced receptor mRNA expression are detected in leprechaunism, Rabson-Mendenhall syndrome, or the type-A syndrome of IR 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 121, 122 . On the other hand polymorphism of IRS-1 like G972R 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 123, 124 or T608R missense mutation 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 125 are observed in patients with T2D that often leads to decreased insulin signalling, mostly by decreasing PI3K activity. Similar to IRS1, missense mutation at R274H in Akt2 leading to loss of kinase activity is also reported in a patient with T2D 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 126. On the contrary, polymorphisms in the PTEN gene, leading to enhanced activity of the enzyme, resulted in reduced insulin-induced Akt activation in three Japanese type-2 diabetic subjects 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 127. Interestingly, individuals with PTEN haploinsufficiency are obese as well as insulin sensitive, with a decreased risk of T2D but increased risk of cancer 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 128. A gain-of-function mutation (Q84R) in Trb3, a pseudo-kinase which hampers Akt activity, decreases insulin-stimulated Akt phosphorylation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 129, 130. In contrast, a loss of function mutation in AS160 at R363 position detected in a girl with extreme postprandial hyperinsulinemia introduces a premature stop codon which results in a truncated AS160 protein that acts in a dominant-negative manner to reduce glucose transport 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 131. Considerable recent progress has been made in the identification of the loci associated with inheritance of IR. However, further work is required to decipher the functional relationship between these genetic variants and insulin action. Identification and validation of these loci will aid to translate this knowledge into clinical practice and help in the management of pathology related to IR. 1.4.2.Environmental causes of insulin resistance:Identification of genetic markers has generated several hypotheses regarding genetics and insulin action but is unable to explain the significant portion of complications associated with T2D. Numerous environmental factors like unhealthy food, barriers to physical activity, stress and social isolation are some of the factors that act as unexplained drivers in the development of T2D/IR. In fact, Atul Butte and his colleagues designed a pilot study to assess the impact of the environmental factors on IR and noted that there are 266 different factors which can affect the insulin signalling ADDIN EN.CITE <EndNote><Cite><Author>Patel</Author><Year>2010</Year><RecNum>636</RecNum><DisplayText>132</DisplayText><record><rec-number>636</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>636</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Patel, C. J.</author><author>Bhattacharya, J.</author><author>Butte, A. J.</author></authors></contributors><auth-address>Department of Pediatrics and Medicine, Stanford University School of Medicine, Stanford, California, USA.</auth-address><titles><title>An Environment-Wide Association Study (EWAS) on type 2 diabetes mellitus</title><secondary-title>PLoS One</secondary-title><alt-title>PloS one</alt-title></titles><periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></periodical><alt-periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></alt-periodical><pages>e10746</pages><volume>5</volume><number>5</number><keywords><keyword>Carotenoids/blood</keyword><keyword>Cohort Studies</keyword><keyword>Diabetes Mellitus, Type 2/*blood</keyword><keyword>*Environment</keyword><keyword>Genetics, Population</keyword><keyword>Health Surveys</keyword><keyword>Humans</keyword><keyword>Pesticides/blood</keyword><keyword>Polychlorinated Biphenyls/blood</keyword><keyword>Reproducibility of Results</keyword><keyword>gamma-Tocopherol/blood</keyword></keywords><dates><year>2010</year><pub-dates><date>May 20</date></pub-dates></dates><isbn>1932-6203 (Electronic) 1932-6203 (Linking)</isbn><accession-num>20505766</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20505766</url></related-urls></urls><custom2>2873978</custom2><electronic-resource-num>10.1371/journal.pone.0010746</electronic-resource-num></record></Cite></EndNote>132. Some of these physiological parameters that play a central role in developing IR are noted in brief below. Circadian Rhythm: Almost all physiological responses are synchronised by the day-night rhythm. Circadian asynchrony in humans due to factors such as work in shifts, jet lag, and/or sleep disruption, can have profound effects on both normal body weights as well as on glucose/lipid homeostasis. The influence of the circadian clock on insulin secretion and glucose homeostasis is demonstrated by the periodic regulation of the associated hormones like leptin, glucagon, cortisol, growth hormone, catecholamines, 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ADDIN EN.CITE.DATA 133, 134. Another linkage between the physiological clock and IR is revealed by the increased risk of obesity and diabetes due to short sleep duration (due to e.g., insomnia and/or circadian disruption) ADDIN EN.CITE <EndNote><Cite><Author>Knutson</Author><Year>2008</Year><RecNum>641</RecNum><DisplayText>135</DisplayText><record><rec-number>641</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>641</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Knutson, K. L.</author><author>Van Cauter, E.</author></authors></contributors><auth-address>Department of Health Studies, University of Chicago, Chicago, IL 60637, USA.</auth-address><titles><title>Associations between sleep loss and increased risk of obesity and diabetes</title><secondary-title>Ann N Y Acad Sci</secondary-title><alt-title>Annals of the New York Academy of Sciences</alt-title></titles><periodical><full-title>Ann N Y Acad Sci</full-title><abbr-1>Annals of the New York Academy of Sciences</abbr-1></periodical><alt-periodical><full-title>Ann N Y Acad Sci</full-title><abbr-1>Annals of the New York Academy of Sciences</abbr-1></alt-periodical><pages>287-304</pages><volume>1129</volume><keywords><keyword>Appetite/physiology</keyword><keyword>Diabetes Mellitus/*etiology/*physiopathology</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Obesity/*complications/*physiopathology</keyword><keyword>Risk Factors</keyword><keyword>Sleep Deprivation/*complications/epidemiology/*physiopathology</keyword></keywords><dates><year>2008</year></dates><isbn>0077-8923 (Print) 0077-8923 (Linking)</isbn><accession-num>18591489</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18591489</url></related-urls></urls><custom2>4394987</custom2><electronic-resource-num>10.1196/annals.1417.033</electronic-resource-num></record></Cite></EndNote>135. Food intake and physical activity: The epidemic of obesity is an unintended biological consequence arising resulting from the imbalance between energy consumed and energy burnt ADDIN EN.CITE <EndNote><Cite><Author>Hill</Author><Year>2006</Year><RecNum>644</RecNum><DisplayText>136</DisplayText><record><rec-number>644</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>644</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Hill, J. O.</author></authors></contributors><auth-address>Center for Human Nutrition, University of Colorado School of Medicine, Denver, Colorado 80262, USA. [email protected]</auth-address><titles><title>Understanding and addressing the epidemic of obesity: an energy balance perspective</title><secondary-title>Endocr Rev</secondary-title><alt-title>Endocrine reviews</alt-title></titles><periodical><full-title>Endocr Rev</full-title><abbr-1>Endocrine reviews</abbr-1></periodical><alt-periodical><full-title>Endocr Rev</full-title><abbr-1>Endocrine reviews</abbr-1></alt-periodical><pages>750-61</pages><volume>27</volume><number>7</number><keywords><keyword>Disease Outbreaks/*prevention & control</keyword><keyword>Energy Metabolism/genetics/*physiology</keyword><keyword>Global Health</keyword><keyword>Humans</keyword><keyword>Motor Activity/physiology</keyword><keyword>Obesity/*epidemiology/genetics/*physiopathology/therapy</keyword><keyword>Social Environment</keyword><keyword>Weight Gain/genetics/physiology</keyword></keywords><dates><year>2006</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0163-769X (Print) 0163-769X (Linking)</isbn><accession-num>17122359</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17122359</url></related-urls></urls><electronic-resource-num>10.1210/er.2006-0032</electronic-resource-num></record></Cite></EndNote>136. Overeating not only includes the presentation of a large quantity of food but also easy access to food, social acceptance and minimal information about the energy content of the food. Contrary to food availability, physical activity has declined steadily in the last 50 years due to enhanced sedentary activities, thus resulting in burning fewer calories. Thus the imbalance generated due to improper energy burning leads to an alteration in the endocrine systems regulating the energy homeostasis, resulting in IR ADDIN EN.CITE <EndNote><Cite><Author>Kim</Author><Year>2010</Year><RecNum>645</RecNum><DisplayText>137</DisplayText><record><rec-number>645</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>645</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Kim, S. H.</author><author>Reaven, G.</author></authors></contributors><auth-address>Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. [email protected]</auth-address><titles><title>Obesity and insulin resistance: an ongoing saga</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>2105-6</pages><volume>59</volume><number>9</number><keywords><keyword>Adipose Tissue/anatomy & histology</keyword><keyword>Humans</keyword><keyword>Hypertrophy/epidemiology</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Obesity/complications/*epidemiology</keyword><keyword>Obesity, Abdominal/epidemiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1939-327X (Electronic) 0012-1797 (Linking)</isbn><accession-num>20805385</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20805385</url></related-urls></urls><custom2>2927930</custom2><electronic-resource-num>10.2337/db10-0766</electronic-resource-num></record></Cite></EndNote>137. Endocrine disruptors: Environmental chemicals are known to impair the functioning of the endocrine system associated with human fertility and reproductive toxicity ADDIN EN.CITE <EndNote><Cite><Author>Olea</Author><Year>2007</Year><RecNum>646</RecNum><DisplayText>138</DisplayText><record><rec-number>646</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>646</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Olea, N.</author><author>Fernandez, M. F.</author></authors></contributors><auth-address>Lab Medical Investigations, Hospital S Cecilio-University of Granada, Granada, Spain. [email protected]</auth-address><titles><title>Chemicals in the environment and human male fertility</title><secondary-title>Occup Environ Med</secondary-title><alt-title>Occupational and environmental medicine</alt-title></titles><periodical><full-title>Occup Environ Med</full-title><abbr-1>Occupational and environmental medicine</abbr-1></periodical><alt-periodical><full-title>Occup Environ Med</full-title><abbr-1>Occupational and environmental medicine</abbr-1></alt-periodical><pages>430-1</pages><volume>64</volume><number>7</number><keywords><keyword>Air Pollutants, Occupational/toxicity</keyword><keyword>Endocrine Disruptors/toxicity</keyword><keyword>Environmental Pollution/*adverse effects</keyword><keyword>Humans</keyword><keyword>Infertility, Male/*chemically induced</keyword><keyword>Male</keyword><keyword>Occupational Exposure</keyword><keyword>Sperm Count</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1470-7926 (Electronic) 1351-0711 (Linking)</isbn><accession-num>17582086</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17582086</url></related-urls></urls><custom2>2078473</custom2><electronic-resource-num>10.1136/oem.2007.033621</electronic-resource-num></record></Cite></EndNote>138. Endocrine disruptors are chemically active ingredients includes estrogen receptor agonist biphenol A (BPA (commonly used in plastic water bottles and microwave resistant plastic wear) and androgen receptor agonist phthalates (generally used in PVC water pipes). As a consequence of the alteration in steroid receptor activities, a deregulation in adipocytes differentiation is noted which may alter the insulin sensitivity leading to its resistance ADDIN EN.CITE <EndNote><Cite><Author>Kelishadi</Author><Year>2013</Year><RecNum>672</RecNum><DisplayText>139</DisplayText><record><rec-number>672</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>672</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Kelishadi, R.</author><author>Poursafa, P.</author><author>Jamshidi, F.</author></authors></contributors><auth-address>Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan 81676-36954, Iran.</auth-address><titles><title>Role of environmental chemicals in obesity: a systematic review on the current evidence</title><secondary-title>J Environ Public Health</secondary-title><alt-title>Journal of environmental and public health</alt-title></titles><periodical><full-title>J Environ Public Health</full-title><abbr-1>Journal of environmental and public health</abbr-1></periodical><alt-periodical><full-title>J Environ Public Health</full-title><abbr-1>Journal of environmental and public health</abbr-1></alt-periodical><pages>896789</pages><volume>2013</volume><keywords><keyword>Animals</keyword><keyword>Environmental Pollutants/*toxicity</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Mice</keyword><keyword>Obesity/*chemically induced/epidemiology</keyword><keyword>Prevalence</keyword></keywords><dates><year>2013</year></dates><isbn>1687-9813 (Electronic) 1687-9805 (Linking)</isbn><accession-num>23840234</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23840234</url></related-urls></urls><custom2>3687513</custom2><electronic-resource-num>10.1155/2013/896789</electronic-resource-num></record></Cite></EndNote>139 . Stress: Stress is the body’s response to a threat, often called the “fight-or-flight” response. In recent years, the roles of chronic stress and/or depression as an independent risk factor for decreased insulin sensitivity and development of diabetes is gaining recognition ADDIN EN.CITE ;EndNote;;Cite;;Author;Kelly;/Author;;Year;2015;/Year;;RecNum;647;/RecNum;;DisplayText;140;/DisplayText;;record;;rec-number;647;/rec-number;;foreign-keys;;key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”;647;/key;;/foreign-keys;;ref-type name=”Journal Article”;17;/ref-type;;contributors;;authors;;author;Kelly, S. J.;/author;;author;Ismail, M.;/author;;/authors;;/contributors;;auth-address;Center for Health and Social Care Research, Sheffield Hallam University, Sheffield S10 2BP, United Kingdom; email: [email protected].;/auth-address;;titles;;title;Stress and type 2 diabetes: a review of how stress contributes to the development of type 2 diabetes;/title;;secondary-title;Annu Rev Public Health;/secondary-title;;alt-title;Annual review of public health;/alt-title;;/titles;;periodical;;full-title;Annu Rev Public Health;/full-title;;abbr-1;Annual review of public health;/abbr-1;;/periodical;;alt-periodical;;full-title;Annu Rev Public Health;/full-title;;abbr-1;Annual review of public health;/abbr-1;;/alt-periodical;;pages;441-62;/pages;;volume;36;/volume;;keywords;;keyword;Aggression/psychology;/keyword;;keyword;Conflict (Psychology);/keyword;;keyword;Diabetes Mellitus, Type 2/*etiology/psychology</keyword><keyword>Humans</keyword><keyword>Mental Disorders/complications</keyword><keyword>Psychology</keyword><keyword>Risk Factors</keyword><keyword>Socioeconomic Factors</keyword><keyword>Stress, Psychological/*complications</keyword></keywords><dates><year>2015</year><pub-dates><date>Mar 18</date></pub-dates></dates><isbn>1545-2093 (Electronic) 0163-7525 (Linking)</isbn><accession-num>25581145</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25581145</url></related-urls></urls><electronic-resource-num>10.1146/annurev-publhealth-031914-122921</electronic-resource-num></record></Cite></EndNote>140. However, the underlying mechanisms linking IR and acute psychological stress are very limited. Stress hormones, particularly cortisol, raise blood glucose levels and blood pressure to provide muscle with sufficient energy required for flight or fight response ADDIN EN.CITE <EndNote><Cite><Author>Ayada</Author><Year>2015</Year><RecNum>669</RecNum><DisplayText>141</DisplayText><record><rec-number>669</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>669</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ayada, C.</author><author>Toru, U.</author><author>Korkut, Y.</author></authors></contributors><auth-address>Department of Physiology, Medical Faculty, Dumlupinar University, Kutahya, Turkey. Department of Chest Diseases, Medical Faculty, Dumlupinar University, Kutahya, Turkey. Department of Family Medicine, Medical Faculty, Dumlupinar University, Kutahya, Turkey.</auth-address><titles><title>The relationship of stress and blood pressure effectors</title><secondary-title>Hippokratia</secondary-title><alt-title>Hippokratia</alt-title></titles><periodical><full-title>Hippokratia</full-title><abbr-1>Hippokratia</abbr-1></periodical><alt-periodical><full-title>Hippokratia</full-title><abbr-1>Hippokratia</abbr-1></alt-periodical><pages>99-108</pages><volume>19</volume><number>2</number><dates><year>2015</year><pub-dates><date>Apr-Jun</date></pub-dates></dates><isbn>1108-4189 (Print) 1108-4189 (Linking)</isbn><accession-num>27418756</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/27418756</url></related-urls></urls><custom2>4938117</custom2></record></Cite></EndNote>141. Cortisol also acts on the liver to enhance hepatic glucose output for sustained muscular activity. Interestingly, stress is a life-saving response, but with modern times, chronic stress has emerged as a prime driver for the development of IR 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ADDIN EN.CITE.DATA 142.1.4.3. Molecular causes of insulin resistance:1.4.3.a. Lipotoxicity/ dyslipidemia:Lipotoxicity is a pathological condition of ectopic accumulation of lipids, especially fatty acids in non-adipose tissues that causes functional impairments in several metabolic pathways and thus plays a central role in the development of IR as well as pancreatic beta cell dysfunction ADDIN EN.CITE <EndNote><Cite><Author>Biden</Author><Year>2014</Year><RecNum>648</RecNum><DisplayText>143</DisplayText><record><rec-number>648</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>648</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Biden, T. J.</author><author>Boslem, E.</author><author>Chu, K. Y.</author><author>Sue, N.</author></authors></contributors><auth-address>Diabetes and Obesity Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. Electronic address: [email protected]. Diabetes and Obesity Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.</auth-address><titles><title>Lipotoxic endoplasmic reticulum stress, beta cell failure, and type 2 diabetes mellitus</title><secondary-title>Trends Endocrinol Metab</secondary-title><alt-title>Trends in endocrinology and metabolism: TEM</alt-title></titles><periodical><full-title>Trends Endocrinol Metab</full-title><abbr-1>Trends in endocrinology and metabolism: TEM</abbr-1></periodical><alt-periodical><full-title>Trends Endocrinol Metab</full-title><abbr-1>Trends in endocrinology and metabolism: TEM</abbr-1></alt-periodical><pages>389-98</pages><volume>25</volume><number>8</number><keywords><keyword>Animals</keyword><keyword>Apoptosis/physiology</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>Endoplasmic Reticulum Stress/*physiology</keyword><keyword>Insulin-Secreting Cells/*metabolism</keyword><keyword>Unfolded Protein Response/physiology</keyword></keywords><dates><year>2014</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1879-3061 (Electronic) 1043-2760 (Linking)</isbn><accession-num>24656915</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24656915</url></related-urls></urls><electronic-resource-num>10.1016/j.tem.2014.02.003</electronic-resource-num></record></Cite></EndNote>143. IR and T2D patients are associated with abnormal lipid metabolism with elevated levels of circulatory concentration of free fatty acid (FFA) and excess lipid deposition in the skeletal muscle 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ADDIN EN.CITE.DATA 144. Increase in plasma FFA reduces insulin-stimulated glucose uptake and inhibits insulin-mediated PI3-kinase activity in skeletal muscle ADDIN EN.CITE <EndNote><Cite><Author>DeFronzo</Author><Year>2009</Year><RecNum>360</RecNum><DisplayText>145</DisplayText><record><rec-number>360</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>360</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>DeFronzo, R. A.</author><author>Tripathy, D.</author></authors></contributors><auth-address>University of Texas Health Science Center, San Antonio, Texas, USA. [email protected]</auth-address><titles><title>Skeletal muscle insulin resistance is the primary defect in type 2 diabetes</title><secondary-title>Diabetes Care</secondary-title><alt-title>Diabetes care</alt-title></titles><periodical><full-title>Diabetes Care</full-title><abbr-1>Diabetes care</abbr-1></periodical><alt-periodical><full-title>Diabetes Care</full-title><abbr-1>Diabetes care</abbr-1></alt-periodical><pages>S157-63</pages><volume>32 Suppl 2</volume><keywords><keyword>Blood Glucose/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/*physiopathology</keyword><keyword>Fatty Acids, Nonesterified/metabolism</keyword><keyword>Glucose Clamp Technique</keyword><keyword>Homeostasis</keyword><keyword>Humans</keyword><keyword>Insulin/physiology/secretion</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Muscle, Skeletal/*physiopathology</keyword></keywords><dates><year>2009</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1935-5548 (Electronic) 0149-5992 (Linking)</isbn><accession-num>19875544</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19875544</url></related-urls></urls><custom2>2811436</custom2><electronic-resource-num>10.2337/dc09-S302</electronic-resource-num></record></Cite></EndNote>145, whereas reduction of plasma lipid content improves insulin action in the insulin-sensitive organs 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ADDIN EN.CITE.DATA 146. In addition to the above, multiple lipid intermediates were reported to promote IR. Elevated circulating FFA observed in obesity causes IR through activation of negative regulators of insulin signalling like JNK, IKK, and PKC that induces IRS-1 phosphorylation at Ser307 ADDIN EN.CITE <EndNote><Cite><Author>Schenk</Author><Year>2008</Year><RecNum>412</RecNum><DisplayText>147</DisplayText><record><rec-number>412</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>412</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Schenk, S.</author><author>Saberi, M.</author><author>Olefsky, J. M.</author></authors></contributors><auth-address>Department of Medicine, Division of Endocrinology and Metabolism, UCSD, La Jolla, California 92093, USA.</auth-address><titles><title>Insulin sensitivity: modulation by nutrients and inflammation</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>2992-3002</pages><volume>118</volume><number>9</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Animals</keyword><keyword>Body Weight</keyword><keyword>Diabetes Mellitus, Type 2/metabolism</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>Humans</keyword><keyword>Inflammation/*complications</keyword><keyword>Insulin/*metabolism/secretion</keyword><keyword>Insulin Resistance</keyword><keyword>Liver/metabolism</keyword><keyword>Macrophages/metabolism</keyword><keyword>Models, Biological</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Obesity/complications</keyword></keywords><dates><year>2008</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0021-9738 (Print) 0021-9738 (Linking)</isbn><accession-num>18769626</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18769626</url></related-urls></urls><custom2>2522344</custom2><electronic-resource-num>10.1172/JCI34260</electronic-resource-num></record></Cite></EndNote>147. FFA like palmitate promotes IR via induction of ER stress, production of cytokine, and activation of JNK 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 142, 148. In addition, palmitate also activates inflammatory pathways such as NF-kB, inhibition of which reverses lipid-induced IR 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 149, 150. Interestingly, the effect of palmitate on skeletal muscle IR is reversed upon mix-up with oleate, as it changes phospholipids and diacylglycerol (DAG) to triglycerides 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 151. Lipid metabolite DAG (intramyocellular lipid) also leads to muscle IR via IRS-1 Ser307 phosphorylation by activating PKC-? 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 152, while ablation of DAG expression in skeletal muscle and liver protected mice against high-fat-diet-induced IR <EndNote><Cite><Author>Liu</Author><Year>2007</Year><RecNum>418</RecNum><DisplayText>[153-155]</DisplayText><record><rec-number>418</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">418</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu, L.</author><author>Zhang, Y.</author><author>Chen, N.</author><author>Shi, X.</author><author>Tsang, B.</author><author>Yu, Y. H.</author></authors></contributors><auth-address>Department of Medicine, Columbia University, New York, New York 10032, USA.</auth-address><titles><title>Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>1679-89</pages><volume>117</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>DNA Primers/genetics</keyword><keyword>Diabetes Mellitus, Type 2/prevention &amp; control</keyword><keyword>Diacylglycerol O-Acyltransferase/deficiency/*genetics/*metabolism</keyword><keyword>Dietary Fats/administration &amp; dosage</keyword><keyword>Humans</keyword><keyword>Insulin Resistance/genetics/*physiology</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Transgenic</keyword><keyword>Muscle, Skeletal/*metabolism</keyword><keyword>Physical Exertion/physiology</keyword><keyword>Triglycerides/*biosynthesis</keyword><keyword>Up-Regulation</keyword></keywords><dates><year>2007</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>17510710</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17510710</url></related-urls></urls><custom2>1866250</custom2><electronic-resource-num>10.1172/JCI30565</electronic-resource-num></record></Cite><Cite><Author>Ahmadian</Author><Year>2009</Year><RecNum>419</RecNum><record><rec-number>419</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">419</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ahmadian, M.</author><author>Duncan, R. E.</author><author>Varady, K. A.</author><author>Frasson, D.</author><author>Hellerstein, M. K.</author><author>Birkenfeld, A. L.</author><author>Samuel, V. T.</author><author>Shulman, G. I.</author><author>Wang, Y.</author><author>Kang, C.</author><author>Sul, H. S.</author></authors></contributors><auth-address>Department of Nutritional Science and Toxicology, University of California, Berkeley, California, USA.</auth-address><titles><title>Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>855-66</pages><volume>58</volume><number>4</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/cytology/physiology</keyword><keyword>Adipose Tissue/*physiology/*physiopathology</keyword><keyword>Animals</keyword><keyword>Carboxylic Ester Hydrolases/*genetics/physiology</keyword><keyword>Cloning, Molecular</keyword><keyword>*Energy Intake</keyword><keyword>Female</keyword><keyword>Lipase/metabolism</keyword><keyword>Lipolysis</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Inbred CBA</keyword><keyword>Mice, Transgenic</keyword><keyword>Obesity/etiology/*prevention &amp; control</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>RNA/genetics</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Triolein/metabolism</keyword></keywords><dates><year>2009</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1939-327X (Electronic)&#xD;0012-1797 (Linking)</isbn><accession-num>19136649</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19136649</url></related-urls></urls><custom2>2661591</custom2><electronic-resource-num>10.2337/db08-1644</electronic-resource-num></record></Cite><Cite><Author>Samuel</Author><Year>2010</Year><RecNum>420</RecNum><record><rec-number>420</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">420</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Samuel, V. T.</author><author>Petersen, K. F.</author><author>Shulman, G. I.</author></authors></contributors><auth-address>Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536-8012, USA.</auth-address><titles><title>Lipid-induced insulin resistance: unravelling the mechanism</title><secondary-title>Lancet</secondary-title><alt-title>Lancet</alt-title></titles><periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></periodical><alt-periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></alt-periodical><pages>2267-77</pages><volume>375</volume><number>9733</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/metabolism</keyword><keyword>Diglycerides</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Fatty Liver/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Lipids/*physiology</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Obesity/*metabolism</keyword><keyword>Protein Kinase C/metabolism</keyword></keywords><dates><year>2010</year><pub-dates><date>Jun 26</date></pub-dates></dates><isbn>1474-547X (Electronic)&#xD;0140-6736 (Linking)</isbn><accession-num>20609972</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20609972</url></related-urls></urls><custom2>2995547</custom2><electronic-resource-num>10.1016/S0140-6736(10)60408-4</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Liu</Author><Year>2007</Year><RecNum>418</RecNum><DisplayText>[153-155]</DisplayText><record><rec-number>418</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">418</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu, L.</author><author>Zhang, Y.</author><author>Chen, N.</author><author>Shi, X.</author><author>Tsang, B.</author><author>Yu, Y. H.</author></authors></contributors><auth-address>Department of Medicine, Columbia University, New York, New York 10032, USA.</auth-address><titles><title>Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>1679-89</pages><volume>117</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Base Sequence</keyword><keyword>DNA Primers/genetics</keyword><keyword>Diabetes Mellitus, Type 2/prevention &amp; control</keyword><keyword>Diacylglycerol O-Acyltransferase/deficiency/*genetics/*metabolism</keyword><keyword>Dietary Fats/administration &amp; dosage</keyword><keyword>Humans</keyword><keyword>Insulin Resistance/genetics/*physiology</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Transgenic</keyword><keyword>Muscle, Skeletal/*metabolism</keyword><keyword>Physical Exertion/physiology</keyword><keyword>Triglycerides/*biosynthesis</keyword><keyword>Up-Regulation</keyword></keywords><dates><year>2007</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>17510710</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17510710</url></related-urls></urls><custom2>1866250</custom2><electronic-resource-num>10.1172/JCI30565</electronic-resource-num></record></Cite><Cite><Author>Ahmadian</Author><Year>2009</Year><RecNum>419</RecNum><record><rec-number>419</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">419</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ahmadian, M.</author><author>Duncan, R. E.</author><author>Varady, K. A.</author><author>Frasson, D.</author><author>Hellerstein, M. K.</author><author>Birkenfeld, A. L.</author><author>Samuel, V. T.</author><author>Shulman, G. I.</author><author>Wang, Y.</author><author>Kang, C.</author><author>Sul, H. S.</author></authors></contributors><auth-address>Department of Nutritional Science and Toxicology, University of California, Berkeley, California, USA.</auth-address><titles><title>Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>855-66</pages><volume>58</volume><number>4</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/cytology/physiology</keyword><keyword>Adipose Tissue/*physiology/*physiopathology</keyword><keyword>Animals</keyword><keyword>Carboxylic Ester Hydrolases/*genetics/physiology</keyword><keyword>Cloning, Molecular</keyword><keyword>*Energy Intake</keyword><keyword>Female</keyword><keyword>Lipase/metabolism</keyword><keyword>Lipolysis</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Inbred CBA</keyword><keyword>Mice, Transgenic</keyword><keyword>Obesity/etiology/*prevention &amp; control</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>RNA/genetics</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Triolein/metabolism</keyword></keywords><dates><year>2009</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1939-327X (Electronic)&#xD;0012-1797 (Linking)</isbn><accession-num>19136649</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19136649</url></related-urls></urls><custom2>2661591</custom2><electronic-resource-num>10.2337/db08-1644</electronic-resource-num></record></Cite><Cite><Author>Samuel</Author><Year>2010</Year><RecNum>420</RecNum><record><rec-number>420</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">420</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Samuel, V. T.</author><author>Petersen, K. F.</author><author>Shulman, G. I.</author></authors></contributors><auth-address>Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536-8012, USA.</auth-address><titles><title>Lipid-induced insulin resistance: unravelling the mechanism</title><secondary-title>Lancet</secondary-title><alt-title>Lancet</alt-title></titles><periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></periodical><alt-periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1></alt-periodical><pages>2267-77</pages><volume>375</volume><number>9733</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/metabolism</keyword><keyword>Diglycerides</keyword><keyword>Fatty Acids/metabolism</keyword><keyword>Fatty Liver/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Lipids/*physiology</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Obesity/*metabolism</keyword><keyword>Protein Kinase C/metabolism</keyword></keywords><dates><year>2010</year><pub-dates><date>Jun 26</date></pub-dates></dates><isbn>1474-547X (Electronic)&#xD;0140-6736 (Linking)</isbn><accession-num>20609972</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20609972</url></related-urls></urls><custom2>2995547</custom2><electronic-resource-num>10.1016/S0140-6736(10)60408-4</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 153-155. Further, the elevated plasma concentration of another lipid intermediate, sphingolipid ceramide, is observed in obese and diabetic patients with severe IR 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 156. Ceramide cause IR via activating PKC and JNK signalling 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ADDIN EN.CITE.DATA 147, 157 and inhibiting the action of Akt by improving the interaction of Akt with PP2A, and by phosphorylating Akt at Thr-34 by PKC ?, resulting in reduced binding of PIP3 to Akt <EndNote><Cite><Author>Teruel</Author><Year>2001</Year><RecNum>424</RecNum><DisplayText>[158-160]</DisplayText><record><rec-number>424</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">424</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Teruel, T.</author><author>Hernandez, R.</author><author>Lorenzo, M.</author></authors></contributors><auth-address>Departamento de Bioquimica y Biologia Molecular II, Facultad de Farmacia, Universidad Complutense, 28040, Madrid, Spain.</auth-address><titles><title>Ceramide mediates insulin resistance by tumor necrosis factor-alpha in brown adipocytes by maintaining Akt in an inactive dephosphorylated state</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>2563-71</pages><volume>50</volume><number>11</number><keywords><keyword>Adipocytes/*physiology</keyword><keyword>Adipose Tissue, Brown/cytology/*physiology</keyword><keyword>Animals</keyword><keyword>Ceramides/*physiology</keyword><keyword>Fetus</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Phosphorylation</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/antagonists &amp; inhibitors/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Tumor Necrosis Factor-alpha/*physiology</keyword></keywords><dates><year>2001</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>11679435</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11679435</url></related-urls></urls></record></Cite><Cite><Author>Powell</Author><Year>2003</Year><RecNum>425</RecNum><record><rec-number>425</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">425</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Powell, D. J.</author><author>Hajduch, E.</author><author>Kular, G.</author><author>Hundal, H. S.</author></authors></contributors><auth-address>Division of Molecular Physiology, MRC Protein Phosphorylation Unit, MSI/WTB Complex, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.</auth-address><titles><title>Ceramide disables 3-phosphoinositide binding to the pleckstrin homology domain of protein kinase B (PKB)/Akt by a PKCzeta-dependent mechanism</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>7794-808</pages><volume>23</volume><number>21</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Ceramides/*metabolism</keyword><keyword>Enzyme Activation</keyword><keyword>Enzyme Inhibitors/metabolism</keyword><keyword>Insulin/metabolism</keyword><keyword>Macromolecular Substances</keyword><keyword>Models, Molecular</keyword><keyword>Molecular Sequence Data</keyword><keyword>Peptides/genetics/metabolism</keyword><keyword>Phosphatidylinositol Phosphates/chemistry/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Binding</keyword><keyword>Protein Isoforms/metabolism</keyword><keyword>Protein Kinase C/genetics/*metabolism</keyword><keyword>Protein Structure, Tertiary</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/chemistry/genetics/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Rats</keyword><keyword>Recombinant Fusion Proteins/genetics/metabolism</keyword><keyword>Sequence Alignment</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2003</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>14560023</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14560023</url></related-urls></urls><custom2>207567</custom2></record></Cite><Cite><Author>Blouin</Author><Year>2010</Year><RecNum>426</RecNum><record><rec-number>426</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">426</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blouin, C. M.</author><author>Prado, C.</author><author>Takane, K. K.</author><author>Lasnier, F.</author><author>Garcia-Ocana, A.</author><author>Ferre, P.</author><author>Dugail, I.</author><author>Hajduch, E.</author></authors></contributors><auth-address>Centre de Recherche des Cordeliers, INSERM, UMR-S 872, Paris, France.</auth-address><titles><title>Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>600-10</pages><volume>59</volume><number>3</number><keywords><keyword>3T3-L1 Cells</keyword><keyword>Adipocytes/cytology/drug effects/*metabolism</keyword><keyword>Animals</keyword><keyword>Caveolins/metabolism</keyword><keyword>Cell Compartmentation/physiology</keyword><keyword>Cell Membrane/*enzymology</keyword><keyword>Ceramides/*pharmacology</keyword><keyword>Fibroblasts/cytology</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Resistance/physiology</keyword><keyword>Membrane Proteins/drug effects/physiology</keyword><keyword>Mice</keyword><keyword>Palmitates/metabolism/pharmacology</keyword><keyword>Phosphoproteins/drug effects/physiology</keyword><keyword>Protein Kinase C/genetics/metabolism</keyword><keyword>Protein Phosphatase 2/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword><keyword>Signal Transduction/*drug effects/physiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1939-327X (Electronic)&#xD;0012-1797 (Linking)</isbn><accession-num>19959757</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19959757</url></related-urls></urls><custom2>2828662</custom2><electronic-resource-num>10.2337/db09-0897</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Teruel</Author><Year>2001</Year><RecNum>424</RecNum><DisplayText>[158-160]</DisplayText><record><rec-number>424</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">424</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Teruel, T.</author><author>Hernandez, R.</author><author>Lorenzo, M.</author></authors></contributors><auth-address>Departamento de Bioquimica y Biologia Molecular II, Facultad de Farmacia, Universidad Complutense, 28040, Madrid, Spain.</auth-address><titles><title>Ceramide mediates insulin resistance by tumor necrosis factor-alpha in brown adipocytes by maintaining Akt in an inactive dephosphorylated state</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>2563-71</pages><volume>50</volume><number>11</number><keywords><keyword>Adipocytes/*physiology</keyword><keyword>Adipose Tissue, Brown/cytology/*physiology</keyword><keyword>Animals</keyword><keyword>Ceramides/*physiology</keyword><keyword>Fetus</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Phosphorylation</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/antagonists &amp; inhibitors/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Tumor Necrosis Factor-alpha/*physiology</keyword></keywords><dates><year>2001</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>11679435</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11679435</url></related-urls></urls></record></Cite><Cite><Author>Powell</Author><Year>2003</Year><RecNum>425</RecNum><record><rec-number>425</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">425</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Powell, D. J.</author><author>Hajduch, E.</author><author>Kular, G.</author><author>Hundal, H. S.</author></authors></contributors><auth-address>Division of Molecular Physiology, MRC Protein Phosphorylation Unit, MSI/WTB Complex, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.</auth-address><titles><title>Ceramide disables 3-phosphoinositide binding to the pleckstrin homology domain of protein kinase B (PKB)/Akt by a PKCzeta-dependent mechanism</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>7794-808</pages><volume>23</volume><number>21</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Ceramides/*metabolism</keyword><keyword>Enzyme Activation</keyword><keyword>Enzyme Inhibitors/metabolism</keyword><keyword>Insulin/metabolism</keyword><keyword>Macromolecular Substances</keyword><keyword>Models, Molecular</keyword><keyword>Molecular Sequence Data</keyword><keyword>Peptides/genetics/metabolism</keyword><keyword>Phosphatidylinositol Phosphates/chemistry/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Binding</keyword><keyword>Protein Isoforms/metabolism</keyword><keyword>Protein Kinase C/genetics/*metabolism</keyword><keyword>Protein Structure, Tertiary</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/chemistry/genetics/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Rats</keyword><keyword>Recombinant Fusion Proteins/genetics/metabolism</keyword><keyword>Sequence Alignment</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2003</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>14560023</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14560023</url></related-urls></urls><custom2>207567</custom2></record></Cite><Cite><Author>Blouin</Author><Year>2010</Year><RecNum>426</RecNum><record><rec-number>426</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">426</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Blouin, C. M.</author><author>Prado, C.</author><author>Takane, K. K.</author><author>Lasnier, F.</author><author>Garcia-Ocana, A.</author><author>Ferre, P.</author><author>Dugail, I.</author><author>Hajduch, E.</author></authors></contributors><auth-address>Centre de Recherche des Cordeliers, INSERM, UMR-S 872, Paris, France.</auth-address><titles><title>Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>600-10</pages><volume>59</volume><number>3</number><keywords><keyword>3T3-L1 Cells</keyword><keyword>Adipocytes/cytology/drug effects/*metabolism</keyword><keyword>Animals</keyword><keyword>Caveolins/metabolism</keyword><keyword>Cell Compartmentation/physiology</keyword><keyword>Cell Membrane/*enzymology</keyword><keyword>Ceramides/*pharmacology</keyword><keyword>Fibroblasts/cytology</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Resistance/physiology</keyword><keyword>Membrane Proteins/drug effects/physiology</keyword><keyword>Mice</keyword><keyword>Palmitates/metabolism/pharmacology</keyword><keyword>Phosphoproteins/drug effects/physiology</keyword><keyword>Protein Kinase C/genetics/metabolism</keyword><keyword>Protein Phosphatase 2/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword><keyword>Signal Transduction/*drug effects/physiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1939-327X (Electronic)&#xD;0012-1797 (Linking)</isbn><accession-num>19959757</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19959757</url></related-urls></urls><custom2>2828662</custom2><electronic-resource-num>10.2337/db09-0897</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 158-160. In addition, alteration of membrane–lipid composition affects insulin signalling. An increase in the saturated to unsaturated fatty acid ratio is observed in T2D patients and is thought to reduce membrane fluidity and insulin sensitivity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 161, 162. An increased phosphatidylcholine to phosphatidylethanolamine ratio is observed in endoplasmic reticulum which is known to cause activation of ER stress associated with IR 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ADDIN EN.CITE.DATA 163.1.4.3.b.Inflammation:By early1950’s, several studies revealed the role of the obesity-associated chronic state of low-grade inflammation in the promotion of IR ADDIN EN.CITE <EndNote><Cite><Author>Osborn</Author><Year>2012</Year><RecNum>430</RecNum><DisplayText>164</DisplayText><record><rec-number>430</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>430</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Osborn, O.</author><author>Olefsky, J. M.</author></authors></contributors><auth-address>Department of Medicine, Division of Endocrinology and Metabolism, University of California-San Diego, La Jolla, California, USA.</auth-address><titles><title>The cellular and signaling networks linking the immune system and metabolism in disease</title><secondary-title>Nat Med</secondary-title><alt-title>Nature medicine</alt-title></titles><periodical><full-title>Nat Med</full-title><abbr-1>Nature medicine</abbr-1></periodical><alt-periodical><full-title>Nat Med</full-title><abbr-1>Nature medicine</abbr-1></alt-periodical><pages>363-74</pages><volume>18</volume><number>3</number><keywords><keyword>Adipose Tissue/immunology/metabolism</keyword><keyword>Cardiovascular Diseases/complications/immunology/*metabolism</keyword><keyword>Diabetes Mellitus, Type 2/complications/immunology/*metabolism</keyword><keyword>Humans</keyword><keyword>Immune System/*metabolism</keyword><keyword>Inflammation/complications/immunology/*metabolism</keyword><keyword>Insulin Resistance/immunology</keyword><keyword>Macrophages/immunology/*metabolism</keyword><keyword>Metabolic Diseases/*immunology</keyword><keyword>Metabolic Networks and Pathways</keyword><keyword>Obesity/complications</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2012</year><pub-dates><date>Mar 6</date></pub-dates></dates><isbn>1546-170X (Electronic) 1078-8956 (Linking)</isbn><accession-num>22395709</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22395709</url></related-urls></urls><electronic-resource-num>10.1038/nm.2627</electronic-resource-num></record></Cite></EndNote>164 however, the precise physiological events leading to the initiation of the inflammatory response in obesity is still obscure. According to one theory, under a caloric overload condition, massive enlargement of existing adipocytes occurs with limited angiogenesis leading to adipocyte hypertrophy and hyperplasia. This restricts the local oxygen supply leading to cell-autonomous hypoxia that activates cellular stress pathways and cell-autonomous inflammation to promote the release of cytokines and other pro-inflammatory signals. The pro-inflammatory macrophages are infiltered into the adipose tissue in response to the locally secreted chemokines to form the tissue-resident macrophages. These macrophages release cytokines to further activate the inflammatory pathways in neighbouring adipocytes, aggravating inflammation to a systemic level 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Increased secretion of the chemokine-like MCP-1 by adipocytes drives macrophage accumulation in adipose tissues leading to IR 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ADDIN EN.CITE.DATA 166. Deletion of MCP-1 or its receptor CCR2 improved insulin sensitivity and ameliorated inflammation in mice 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 167, 168. Activation of inflammatory pathways like c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-?B) leads to continuous production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-?) and interleukin-6 (IL-6) in obese patients ADDIN EN.CITE <EndNote><Cite><Author>Shoelson</Author><Year>2006</Year><RecNum>512</RecNum><DisplayText>169, 170</DisplayText><record><rec-number>512</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>512</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Shoelson, Steven E</author><author>Lee, Jongsoon</author><author>Goldfine, Allison B</author></authors></contributors><titles><title>Inflammation and insulin resistance</title><secondary-title>The Journal of clinical investigation</secondary-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><pages>1793-1801</pages><volume>116</volume><number>7</number><dates><year>2006</year></dates><isbn>0021-9738</isbn><urls></urls></record></Cite><Cite><Author>Sharma</Author><Year>2013</Year><RecNum>513</RecNum><record><rec-number>513</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>513</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Sharma, Mukti</author><author>Vikram, Naval Kishore</author><author>Misra, Anoop</author><author>Bhatt, SuryaPrakash</author><author>Tarique, Mohammed</author><author>Parray, Hilal Ahmad</author><author>Pandey, Ravindra Mohan</author><author>Luthra, Kalpana</author></authors></contributors><titles><title>Assessment of 11-? hydroxysteroid dehydrogenase (11-?HSD1) 4478T> G and tumor necrosis factor-? (TNF-?)-308G> A polymorphisms with obesity and insulin resistance in Asian Indians in North India</title><secondary-title>Molecular biology reports</secondary-title></titles><periodical><full-title>Mol Biol Rep</full-title><abbr-1>Molecular biology reports</abbr-1></periodical><pages>6261-6270</pages><volume>40</volume><number>11</number><dates><year>2013</year></dates><isbn>0301-4851</isbn><urls></urls></record></Cite></EndNote>169, 170 that are directly or indirectly linked to IR , hypertension and/or glucolipotoxicity <EndNote><Cite><Author>Akash</Author><Year>2012</Year><RecNum>514</RecNum><DisplayText>[171-173]</DisplayText><record><rec-number>514</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">514</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Akash, M. S.</author><author>Shen, Q.</author><author>Rehman, K.</author><author>Chen, S.</author></authors></contributors><auth-address>Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.</auth-address><titles><title>Interleukin-1 receptor antagonist: a new therapy for type 2 diabetes mellitus</title><secondary-title>J Pharm Sci</secondary-title><alt-title>Journal of pharmaceutical sciences</alt-title></titles><periodical><full-title>J Pharm Sci</full-title><abbr-1>Journal of pharmaceutical sciences</abbr-1></periodical><alt-periodical><full-title>J Pharm Sci</full-title><abbr-1>Journal of pharmaceutical sciences</abbr-1></alt-periodical><pages>1647-58</pages><volume>101</volume><number>5</number><keywords><keyword>Anti-Inflammatory Agents/therapeutic use</keyword><keyword>Diabetes Mellitus, Type 2/*drug therapy/physiopathology</keyword><keyword>Drug Approval</keyword><keyword>Half-Life</keyword><keyword>Humans</keyword><keyword>Inflammation Mediators/physiology</keyword><keyword>Interleukin 1 Receptor Antagonist Protein/pharmacokinetics/*therapeutic use</keyword><keyword>Oxidative Stress</keyword><keyword>United States</keyword><keyword>United States Food and Drug Administration</keyword></keywords><dates><year>2012</year><pub-dates><date>May</date></pub-dates></dates><isbn>1520-6017 (Electronic)&#xD;0022-3549 (Linking)</isbn><accession-num>22271340</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22271340</url></related-urls></urls><electronic-resource-num>10.1002/jps.23057</electronic-resource-num></record></Cite><Cite><Author>Akash</Author><Year>2013</Year><RecNum>515</RecNum><record><rec-number>515</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">515</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Akash, M. S.</author><author>Rehman, K.</author><author>Chen, S.</author></authors></contributors><auth-address>Institute of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.</auth-address><titles><title>Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus</title><secondary-title>J Cell Biochem</secondary-title><alt-title>Journal of cellular biochemistry</alt-title></titles><periodical><full-title>J Cell Biochem</full-title><abbr-1>Journal of cellular biochemistry</abbr-1></periodical><alt-periodical><full-title>J Cell Biochem</full-title><abbr-1>Journal of cellular biochemistry</abbr-1></alt-periodical><pages>525-31</pages><volume>114</volume><number>3</number><keywords><keyword>Apoptosis</keyword><keyword>Chemokines</keyword><keyword>Cytokines</keyword><keyword>Diabetes Mellitus, Type 2/immunology/*pathology</keyword><keyword>Dyslipidemias</keyword><keyword>Humans</keyword><keyword>Hyperglycemia</keyword><keyword>Inflammation/immunology/*pathology</keyword><keyword>Inflammation Mediators</keyword><keyword>Insulin/secretion</keyword><keyword>*Insulin Resistance</keyword><keyword>Insulin-Secreting Cells/*pathology</keyword><keyword>Oxidative Stress</keyword></keywords><dates><year>2013</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1097-4644 (Electronic)&#xD;0730-2312 (Linking)</isbn><accession-num>22991242</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22991242</url></related-urls></urls><electronic-resource-num>10.1002/jcb.24402</electronic-resource-num></record></Cite><Cite><Author>Hak</Author><Year>2001</Year><RecNum>516</RecNum><record><rec-number>516</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">516</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hak, A. E.</author><author>Pols, H. A.</author><author>Stehouwer, C. D.</author><author>Meijer, J.</author><author>Kiliaan, A. J.</author><author>Hofman, A.</author><author>Breteler, M. M.</author><author>Witteman, J. C.</author></authors></contributors><auth-address>Department of Epidemiology &amp; Biostatistics, Erasmus Medical Center Rotterdam, 3000 DR Rotterdam, The Netherlands.</auth-address><titles><title>Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study</title><secondary-title>J Clin Endocrinol Metab</secondary-title><alt-title>The Journal of clinical endocrinology and metabolism</alt-title></titles><periodical><full-title>J Clin Endocrinol Metab</full-title><abbr-1>The Journal of clinical endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>J Clin Endocrinol Metab</full-title><abbr-1>The Journal of clinical endocrinology and metabolism</abbr-1></alt-periodical><pages>4398-405</pages><volume>86</volume><number>9</number><keywords><keyword>Aged</keyword><keyword>Biomarkers</keyword><keyword>C-Reactive Protein/metabolism</keyword><keyword>Cardiovascular Diseases/epidemiology</keyword><keyword>Cell Adhesion Molecules/*metabolism</keyword><keyword>Cohort Studies</keyword><keyword>Endothelium, Vascular/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Inflammation/epidemiology/metabolism/*pathology</keyword><keyword>Insulin/blood</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Interleukin-6/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Netherlands/epidemiology</keyword><keyword>Population</keyword><keyword>Sex Factors</keyword><keyword>alpha 1-Antichymotrypsin/blood</keyword></keywords><dates><year>2001</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0021-972X (Print)&#xD;0021-972X (Linking)</isbn><accession-num>11549682</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11549682</url></related-urls></urls><electronic-resource-num>10.1210/jcem.86.9.7873</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Akash</Author><Year>2012</Year><RecNum>514</RecNum><DisplayText>[171-173]</DisplayText><record><rec-number>514</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">514</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Akash, M. S.</author><author>Shen, Q.</author><author>Rehman, K.</author><author>Chen, S.</author></authors></contributors><auth-address>Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.</auth-address><titles><title>Interleukin-1 receptor antagonist: a new therapy for type 2 diabetes mellitus</title><secondary-title>J Pharm Sci</secondary-title><alt-title>Journal of pharmaceutical sciences</alt-title></titles><periodical><full-title>J Pharm Sci</full-title><abbr-1>Journal of pharmaceutical sciences</abbr-1></periodical><alt-periodical><full-title>J Pharm Sci</full-title><abbr-1>Journal of pharmaceutical sciences</abbr-1></alt-periodical><pages>1647-58</pages><volume>101</volume><number>5</number><keywords><keyword>Anti-Inflammatory Agents/therapeutic use</keyword><keyword>Diabetes Mellitus, Type 2/*drug therapy/physiopathology</keyword><keyword>Drug Approval</keyword><keyword>Half-Life</keyword><keyword>Humans</keyword><keyword>Inflammation Mediators/physiology</keyword><keyword>Interleukin 1 Receptor Antagonist Protein/pharmacokinetics/*therapeutic use</keyword><keyword>Oxidative Stress</keyword><keyword>United States</keyword><keyword>United States Food and Drug Administration</keyword></keywords><dates><year>2012</year><pub-dates><date>May</date></pub-dates></dates><isbn>1520-6017 (Electronic)&#xD;0022-3549 (Linking)</isbn><accession-num>22271340</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22271340</url></related-urls></urls><electronic-resource-num>10.1002/jps.23057</electronic-resource-num></record></Cite><Cite><Author>Akash</Author><Year>2013</Year><RecNum>515</RecNum><record><rec-number>515</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">515</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Akash, M. S.</author><author>Rehman, K.</author><author>Chen, S.</author></authors></contributors><auth-address>Institute of Pharmacology, Toxicology, and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.</auth-address><titles><title>Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus</title><secondary-title>J Cell Biochem</secondary-title><alt-title>Journal of cellular biochemistry</alt-title></titles><periodical><full-title>J Cell Biochem</full-title><abbr-1>Journal of cellular biochemistry</abbr-1></periodical><alt-periodical><full-title>J Cell Biochem</full-title><abbr-1>Journal of cellular biochemistry</abbr-1></alt-periodical><pages>525-31</pages><volume>114</volume><number>3</number><keywords><keyword>Apoptosis</keyword><keyword>Chemokines</keyword><keyword>Cytokines</keyword><keyword>Diabetes Mellitus, Type 2/immunology/*pathology</keyword><keyword>Dyslipidemias</keyword><keyword>Humans</keyword><keyword>Hyperglycemia</keyword><keyword>Inflammation/immunology/*pathology</keyword><keyword>Inflammation Mediators</keyword><keyword>Insulin/secretion</keyword><keyword>*Insulin Resistance</keyword><keyword>Insulin-Secreting Cells/*pathology</keyword><keyword>Oxidative Stress</keyword></keywords><dates><year>2013</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1097-4644 (Electronic)&#xD;0730-2312 (Linking)</isbn><accession-num>22991242</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22991242</url></related-urls></urls><electronic-resource-num>10.1002/jcb.24402</electronic-resource-num></record></Cite><Cite><Author>Hak</Author><Year>2001</Year><RecNum>516</RecNum><record><rec-number>516</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">516</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hak, A. E.</author><author>Pols, H. A.</author><author>Stehouwer, C. D.</author><author>Meijer, J.</author><author>Kiliaan, A. J.</author><author>Hofman, A.</author><author>Breteler, M. M.</author><author>Witteman, J. C.</author></authors></contributors><auth-address>Department of Epidemiology &amp; Biostatistics, Erasmus Medical Center Rotterdam, 3000 DR Rotterdam, The Netherlands.</auth-address><titles><title>Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study</title><secondary-title>J Clin Endocrinol Metab</secondary-title><alt-title>The Journal of clinical endocrinology and metabolism</alt-title></titles><periodical><full-title>J Clin Endocrinol Metab</full-title><abbr-1>The Journal of clinical endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>J Clin Endocrinol Metab</full-title><abbr-1>The Journal of clinical endocrinology and metabolism</abbr-1></alt-periodical><pages>4398-405</pages><volume>86</volume><number>9</number><keywords><keyword>Aged</keyword><keyword>Biomarkers</keyword><keyword>C-Reactive Protein/metabolism</keyword><keyword>Cardiovascular Diseases/epidemiology</keyword><keyword>Cell Adhesion Molecules/*metabolism</keyword><keyword>Cohort Studies</keyword><keyword>Endothelium, Vascular/physiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Inflammation/epidemiology/metabolism/*pathology</keyword><keyword>Insulin/blood</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Interleukin-6/blood</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Netherlands/epidemiology</keyword><keyword>Population</keyword><keyword>Sex Factors</keyword><keyword>alpha 1-Antichymotrypsin/blood</keyword></keywords><dates><year>2001</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0021-972X (Print)&#xD;0021-972X (Linking)</isbn><accession-num>11549682</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11549682</url></related-urls></urls><electronic-resource-num>10.1210/jcem.86.9.7873</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 171-173. In addition to adipose tissue, the effect of released pro-inflammatory cytokines including adipokines such as TNF-? is also observed in liver and muscle 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 174, 175. TNF-? produced by adipose tissue induces IR by enhancing adipocyte lipolysis and increasing the serine/threonine phosphorylation of IRS-1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 174, 176. However, the role of TNF-? in adipose glucose metabolism is controversial. TNF-? is reported to promote uptake of glucose by activating AMPK in both visceral and subcutaneous adipocytes, while causes IR by activating JNK1/2 in visceral adipocytes. Hence, the approaches to treat IR by modulating TNF-? signalling are still on-going 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 177. However, therapies aimed to block TNF-? signalling by using TNF-? superfamily member sTWEAK (soluble tumour necrosis factor-like weak inducer of apoptosis) have demonstrated the role TNF-? in IR 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ADDIN EN.CITE.DATA 178. Other than TNF-?, increased secretion of other cytokines, such as IL-1? or IL-6 , by both immune cells and adipocytes also induces IR via multiple mechanisms, including activation of Ser/Thr kinases <EndNote><Cite><Author>Ozes</Author><Year>2001</Year><RecNum>399</RecNum><DisplayText>[100, 103, 179, 180]</DisplayText><record><rec-number>399</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">399</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozes, O. N.</author><author>Akca, H.</author><author>Mayo, L. D.</author><author>Gustin, J. A.</author><author>Maehama, T.</author><author>Dixon, J. E.</author><author>Donner, D. B.</author></authors></contributors><auth-address>Department of Microbiology and Immunology, Indiana University School of Medicine and the Walther Oncology Center, Indianapolis, IN 46202, USA.</auth-address><titles><title>A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>4640-5</pages><volume>98</volume><number>8</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Cell Line</keyword><keyword>Chromatography, Liquid</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance</keyword><keyword>Molecular Sequence Data</keyword><keyword>PTEN Phosphohydrolase</keyword><keyword>Phosphatidylinositol 3-Kinases/*metabolism</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Phosphoric Monoester Hydrolases/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Phosphotransferases (Alcohol Group Acceptor)/*metabolism</keyword><keyword>*Protein Kinases</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>*Signal Transduction</keyword><keyword>Spectrometry, Mass, Electrospray Ionization</keyword><keyword>TOR Serine-Threonine Kinases</keyword><keyword>Tumor Necrosis Factor-alpha/*antagonists &amp; inhibitors</keyword><keyword>*Tumor Suppressor Proteins</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr 10</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>11287630</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11287630</url></related-urls></urls><custom2>31887</custom2><electronic-resource-num>10.1073/pnas.051042298</electronic-resource-num></record></Cite><Cite><Author>Hirosumi</Author><Year>2002</Year><RecNum>436</RecNum><record><rec-number>436</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">436</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hirosumi, J.</author><author>Tuncman, G.</author><author>Chang, L.</author><author>Gorgun, C. Z.</author><author>Uysal, K. T.</author><author>Maeda, K.</author><author>Karin, M.</author><author>Hotamisligil, G. 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J.</author><author>Ye, J.</author></authors></contributors><auth-address>Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.</auth-address><titles><title>S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>35375-82</pages><volume>283</volume><number>51</number><keywords><keyword>Adipocytes/enzymology</keyword><keyword>Adipose Tissue/enzymology</keyword><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Gene Knockdown Techniques</keyword><keyword>Hepatocytes/enzymology</keyword><keyword>Humans</keyword><keyword>I-kappa B Kinase/genetics/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins/genetics/*metabolism</keyword><keyword>*Insulin Resistance/genetics</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>Phosphorylation/genetics</keyword><keyword>Point Mutation</keyword><keyword>Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism</keyword><keyword>*Signal Transduction/genetics</keyword><keyword>Tumor Necrosis Factor-alpha/genetics/*metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Dec 19</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>18952604</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18952604</url></related-urls></urls><custom2>2602883</custom2><electronic-resource-num>10.1074/jbc.M806480200</electronic-resource-num></record></Cite><Cite><Author>Fan</Author><Year>2010</Year><RecNum>438</RecNum><record><rec-number>438</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">438</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fan, Y.</author><author>Yu, Y.</author><author>Shi, Y.</author><author>Sun, W.</author><author>Xie, M.</author><author>Ge, N.</author><author>Mao, R.</author><author>Chang, A.</author><author>Xu, G.</author><author>Schneider, M. 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N.</author><author>Akca, H.</author><author>Mayo, L. D.</author><author>Gustin, J. A.</author><author>Maehama, T.</author><author>Dixon, J. E.</author><author>Donner, D. B.</author></authors></contributors><auth-address>Department of Microbiology and Immunology, Indiana University School of Medicine and the Walther Oncology Center, Indianapolis, IN 46202, USA.</auth-address><titles><title>A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>4640-5</pages><volume>98</volume><number>8</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Cell Line</keyword><keyword>Chromatography, Liquid</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance</keyword><keyword>Molecular Sequence Data</keyword><keyword>PTEN Phosphohydrolase</keyword><keyword>Phosphatidylinositol 3-Kinases/*metabolism</keyword><keyword>Phosphoproteins/*metabolism</keyword><keyword>Phosphoric Monoester Hydrolases/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Phosphotransferases (Alcohol Group Acceptor)/*metabolism</keyword><keyword>*Protein Kinases</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Proto-Oncogene Proteins/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>*Signal Transduction</keyword><keyword>Spectrometry, Mass, Electrospray Ionization</keyword><keyword>TOR Serine-Threonine Kinases</keyword><keyword>Tumor Necrosis Factor-alpha/*antagonists &amp; inhibitors</keyword><keyword>*Tumor Suppressor Proteins</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Apr 10</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>11287630</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11287630</url></related-urls></urls><custom2>31887</custom2><electronic-resource-num>10.1073/pnas.051042298</electronic-resource-num></record></Cite><Cite><Author>Hirosumi</Author><Year>2002</Year><RecNum>436</RecNum><record><rec-number>436</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">436</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hirosumi, J.</author><author>Tuncman, G.</author><author>Chang, L.</author><author>Gorgun, C. Z.</author><author>Uysal, K. T.</author><author>Maeda, K.</author><author>Karin, M.</author><author>Hotamisligil, G. S.</author></authors></contributors><auth-address>Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA.</auth-address><titles><title>A central role for JNK in obesity and insulin resistance</title><secondary-title>Nature</secondary-title><alt-title>Nature</alt-title></titles><periodical><full-title>Nature</full-title><abbr-1>Nature</abbr-1></periodical><alt-periodical><full-title>Nature</full-title><abbr-1>Nature</abbr-1></alt-periodical><pages>333-6</pages><volume>420</volume><number>6913</number><keywords><keyword>Adipose Tissue/enzymology/metabolism/physiopathology</keyword><keyword>Animals</keyword><keyword>Blood Glucose/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/complications/enzymology/genetics/physiopathology</keyword><keyword>Diet</keyword><keyword>Disease Models, Animal</keyword><keyword>Gene Deletion</keyword><keyword>Homeostasis</keyword><keyword>Hyperinsulinism/complications/enzymology/genetics/physiopathology</keyword><keyword>Insulin/pharmacology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Insulin Resistance/genetics/*physiology</keyword><keyword>Lipid Metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Obese</keyword><keyword>Mitogen-Activated Protein Kinase 8</keyword><keyword>Mitogen-Activated Protein Kinase 9</keyword><keyword>Mitogen-Activated Protein Kinases/deficiency/genetics/*metabolism</keyword><keyword>Obesity/complications/*enzymology/genetics/*physiopathology</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Signal Transduction/drug effects</keyword></keywords><dates><year>2002</year><pub-dates><date>Nov 21</date></pub-dates></dates><isbn>0028-0836 (Print)&#xD;0028-0836 (Linking)</isbn><accession-num>12447443</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12447443</url></related-urls></urls><electronic-resource-num>10.1038/nature01137</electronic-resource-num></record></Cite><Cite><Author>Zhang</Author><Year>2008</Year><RecNum>316</RecNum><record><rec-number>316</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">316</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhang, J.</author><author>Gao, Z.</author><author>Yin, J.</author><author>Quon, M. J.</author><author>Ye, J.</author></authors></contributors><auth-address>Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.</auth-address><titles><title>S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>35375-82</pages><volume>283</volume><number>51</number><keywords><keyword>Adipocytes/enzymology</keyword><keyword>Adipose Tissue/enzymology</keyword><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Gene Knockdown Techniques</keyword><keyword>Hepatocytes/enzymology</keyword><keyword>Humans</keyword><keyword>I-kappa B Kinase/genetics/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins/genetics/*metabolism</keyword><keyword>*Insulin Resistance/genetics</keyword><keyword>Mice</keyword><keyword>Mice, Obese</keyword><keyword>Phosphorylation/genetics</keyword><keyword>Point Mutation</keyword><keyword>Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism</keyword><keyword>*Signal Transduction/genetics</keyword><keyword>Tumor Necrosis Factor-alpha/genetics/*metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Dec 19</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>18952604</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18952604</url></related-urls></urls><custom2>2602883</custom2><electronic-resource-num>10.1074/jbc.M806480200</electronic-resource-num></record></Cite><Cite><Author>Fan</Author><Year>2010</Year><RecNum>438</RecNum><record><rec-number>438</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">438</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fan, Y.</author><author>Yu, Y.</author><author>Shi, Y.</author><author>Sun, W.</author><author>Xie, M.</author><author>Ge, N.</author><author>Mao, R.</author><author>Chang, A.</author><author>Xu, G.</author><author>Schneider, M. D.</author><author>Zhang, H.</author><author>Fu, S.</author><author>Qin, J.</author><author>Yang, J.</author></authors></contributors><auth-address>Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China.</auth-address><titles><title>Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor necrosis factor alpha- and interleukin-1beta-induced IKK/NF-kappaB and JNK/AP-1 activation</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>5347-60</pages><volume>285</volume><number>8</number><keywords><keyword>Amino Acid Substitution</keyword><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Embryo, Mammalian/metabolism</keyword><keyword>Fibroblasts/metabolism</keyword><keyword>Humans</keyword><keyword>I-kappa B Kinase/genetics/*metabolism</keyword><keyword>Interleukin-1beta/*metabolism/pharmacology</keyword><keyword>Interleukin-6/biosynthesis/genetics</keyword><keyword>JNK Mitogen-Activated Protein Kinases/genetics/*metabolism</keyword><keyword>Lysine/genetics/*metabolism</keyword><keyword>MAP Kinase Kinase Kinases/genetics/*metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Mutant Strains</keyword><keyword>Mutation, Missense</keyword><keyword>NF-kappa B/genetics/*metabolism</keyword><keyword>Signal Transduction/drug effects/physiology</keyword><keyword>TNF Receptor-Associated Factor 2/genetics/metabolism</keyword><keyword>TNF Receptor-Associated Factor 6/genetics/metabolism</keyword><keyword>Transcription Factor AP-1/genetics/*metabolism</keyword><keyword>Tumor Necrosis Factor-alpha/*metabolism/pharmacology</keyword><keyword>Ubiquitin-Protein Ligases/genetics/metabolism</keyword><keyword>Ubiquitination/drug effects/*physiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Feb 19</date></pub-dates></dates><isbn>1083-351X (Electronic)&#xD;0021-9258 (Linking)</isbn><accession-num>20038579</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20038579</url></related-urls></urls><custom2>2820763</custom2><electronic-resource-num>10.1074/jbc.M109.076976</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 100, 103, 179, 180, decreasing IRS-1, GLUT4, and PPAR? expression 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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb3R0ZXI8L0F1dGhvcj48WWVhcj4yMDAzPC9ZZWFyPjxSZWNOdW0+NDM5PC9SZWNOdW0+PERpc3BsYXlUZXh0PlsxODEsIDE4Ml08L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+NDM5PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0icGR0c2F2ZWQ3cHB3cjBlMHMycXZ6MnpmMHd4cngyeGQwYWF2Ij40Mzk8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlJvdHRlciwgVi48L2F1dGhvcj48YXV0aG9yPk5hZ2FldiwgSS48L2F1dGhvcj48YXV0aG9yPlNtaXRoLCBVLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRlcGFydG1lbnQgb2YgSW50ZXJuYWwgTWVkaWNpbmUsIEx1bmRiZXJnIExhYm9yYXRvcnkgZm9yIERpYWJldGVzIFJlc2VhcmNoLCBUaGUgU2FobGdyZW5za2EgQWNhZGVteSwgR290ZWJvcmcgVW5pdmVyc2l0eSwgU0UtNDEzIDQ1IEdvdGVib3JnLCBTd2VkZW4uPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+SW50ZXJsZXVraW4tNiAoSUwtNikgaW5kdWNlcyBpbnN1bGluIHJlc2lzdGFuY2UgaW4gM1QzLUwxIGFkaXBvY3l0ZXMgYW5kIGlzLCBsaWtlIElMLTggYW5kIHR1bW9yIG5lY3Jvc2lzIGZhY3Rvci1hbHBoYSwgb3ZlcmV4cHJlc3NlZCBpbiBodW1hbiBmYXQgY2VsbHMgZnJvbSBpbnN1bGluLXJlc2lzdGFudCBzdWJqZWN0czwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIEJpb2wgQ2hlbTwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+VGhlIEpvdXJuYWwgb2YgYmlvbG9naWNhbCBjaGVtaXN0cnk8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEJpb2wgQ2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRoZSBKb3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hlbWlzdHJ5PC9hYmJyLTE+PC9wZXJpb2RpY2FsPjxhbHQtcGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEJpb2wgQ2hlbTwvZnVsbC10aXRsZT48YWJici0xPlRoZSBKb3VybmFsIG9mIGJpb2xvZ2ljYWwgY2hlbWlzdHJ5PC9hYmJyLTE+PC9hbHQtcGVyaW9kaWNhbD48cGFnZXM+NDU3NzctODQ8L3BhZ2VzPjx2b2x1bWU+Mjc4PC92b2x1bWU+PG51bWJlcj40NjwvbnVtYmVyPjxrZXl3b3Jkcz48a2V5d29yZD4zVDMtTDEgQ2VsbHM8L2tleXdvcmQ+PGtleXdvcmQ+QWRpcG9jeXRlcy8qbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5BZGlwb3NlIFRpc3N1ZS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPkFkdWx0PC9rZXl3b3JkPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtleXdvcmQ+QmlvbG9naWNhbCBUcmFuc3BvcnQ8L2tleXdvcmQ+PGtleXdvcmQ+QmxvdHRpbmcsIE5vcnRoZXJuPC9rZXl3b3JkPjxrZXl3b3JkPkN5dG9raW5lcy9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPkRvc2UtUmVzcG9uc2UgUmVsYXRpb25zaGlwLCBEcnVnPC9rZXl3b3JkPjxrZXl3b3JkPkdsdWNvc2UvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5HbHVjb3NlIFRyYW5zcG9ydGVyIFR5cGUgNDwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+SW5zdWxpbiBSZWNlcHRvciBTdWJzdHJhdGUgUHJvdGVpbnM8L2tleXdvcmQ+PGtleXdvcmQ+Kkluc3VsaW4gUmVzaXN0YW5jZTwva2V5d29yZD48a2V5d29yZD5JbnRlcmxldWtpbi02LyptZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPkludGVybGV1a2luLTgvKm1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+KkpOSyBNaXRvZ2VuLUFjdGl2YXRlZCBQcm90ZWluIEtpbmFzZXM8L2tleXdvcmQ+PGtleXdvcmQ+TUFQIEtpbmFzZSBLaW5hc2UgNDwva2V5d29yZD48a2V5d29yZD5NaWNlPC9rZXl3b3JkPjxrZXl3b3JkPk1pZGRsZSBBZ2VkPC9rZXl3b3JkPjxrZXl3b3JkPk1pdG9nZW4tQWN0aXZhdGVkIFByb3RlaW4gS2luYXNlIEtpbmFzZXMvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5Nb25vc2FjY2hhcmlkZSBUcmFuc3BvcnQgUHJvdGVpbnMvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD4qTXVzY2xlIFByb3RlaW5zPC9rZXl3b3JkPjxrZXl3b3JkPlBob3NwaG9wcm90ZWlucy9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlBob3NwaG9yeWxhdGlvbjwva2V5d29yZD48a2V5d29yZD5Qcm90ZWlucy9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlJOQS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlJOQSwgTWVzc2VuZ2VyL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+KlJlcHJlc3NvciBQcm90ZWluczwva2V5d29yZD48a2V5d29yZD5SZXZlcnNlIFRyYW5zY3JpcHRhc2UgUG9seW1lcmFzZSBDaGFpbiBSZWFjdGlvbjwva2V5d29yZD48a2V5d29yZD5TdXBwcmVzc29yIG9mIEN5dG9raW5lIFNpZ25hbGluZyAzIFByb3RlaW48L2tleXdvcmQ+PGtleXdvcmQ+U3VwcHJlc3NvciBvZiBDeXRva2luZSBTaWduYWxpbmcgUHJvdGVpbnM8L2tleXdvcmQ+PGtleXdvcmQ+VGltZSBGYWN0b3JzPC9rZXl3b3JkPjxrZXl3b3JkPipUcmFuc2NyaXB0aW9uIEZhY3RvcnM8L2tleXdvcmQ+PGtleXdvcmQ+VHJhbnNjcmlwdGlvbiwgR2VuZXRpYzwva2V5d29yZD48a2V5d29yZD5UdW1vciBOZWNyb3NpcyBGYWN0b3ItYWxwaGEvKm1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+VHlyb3NpbmUvY2hlbWlzdHJ5L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+VXAtUmVndWxhdGlvbjwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDAzPC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+Tm92IDE0PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAyMS05MjU4IChQcmludCkmI3hEOzAwMjEtOTI1OCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTI5NTI5Njk8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHA6Ly93d3cubmNiaS5ubG0ubmloLmdvdi9wdWJtZWQvMTI5NTI5Njk8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwNzQvamJjLk0zMDE5NzcyMDA8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0ZT48QXV0aG9yPkphZ2VyPC9BdXRob3I+PFllYXI+MjAwNzwvWWVhcj48UmVjTnVtPjQ0MDwvUmVjTnVtPjxyZWNvcmQ+PHJlYy1udW1iZXI+NDQwPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0icGR0c2F2ZWQ3cHB3cjBlMHMycXZ6MnpmMHd4cngyeGQwYWF2Ij40NDA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkphZ2VyLCBKLjwvYXV0aG9yPjxhdXRob3I+R3JlbWVhdXgsIFQuPC9hdXRob3I+PGF1dGhvcj5Db3Jtb250LCBNLjwvYXV0aG9yPjxhdXRob3I+TGUgTWFyY2hhbmQtQnJ1c3RlbCwgWS48L2F1dGhvcj48YXV0aG9yPlRhbnRpLCBKLiBGLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkluc3RpdHV0IE5hdGlvbmFsIGRlIGxhIFNhbnRlIGV0IGRlIGxhIFJlY2hlcmNoZSBNZWRpY2FsZSAoSU5TRVJNKSBVNTY4LCBGYWN1bHR5IG9mIE1lZGljaW5lLCBBdmVudWUg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ADDIN EN.CITE.DATA 181, 182, or activation of SOCS3 in adipocytes 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ADDIN EN.CITE.DATA 183. Further, the ability of dietary fatty acids too activates the inflammatory response via Toll-like receptors (TLR) signalling in cultured macrophages making TLRs a key component of fatty acid-induced inflammation. Stimulation of TLR results in expression and secretion of pro-inflammatory cytokines/chemokines like IL-6, TNF-?, MCP1, etc. via activation of both Ikkb/NF?B and JNK/AP-1 signalling, which may, in turn, lead to IR ADDIN EN.CITE <EndNote><Cite><Author>Chawla</Author><Year>2011</Year><RecNum>521</RecNum><DisplayText>184</DisplayText><record><rec-number>521</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>521</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Chawla, A.</author><author>Nguyen, K. D.</author><author>Goh, Y. P.</author></authors></contributors><auth-address>Cardiovascular Research Institute, University of California San Francisco, California 94158-9001, USA. [email protected]</auth-address><titles><title>Macrophage-mediated inflammation in metabolic disease</title><secondary-title>Nat Rev Immunol</secondary-title><alt-title>Nature reviews. Immunology</alt-title></titles><periodical><full-title>Nat Rev Immunol</full-title><abbr-1>Nature reviews. Immunology</abbr-1></periodical><alt-periodical><full-title>Nat Rev Immunol</full-title><abbr-1>Nature reviews. Immunology</abbr-1></alt-periodical><pages>738-49</pages><volume>11</volume><number>11</number><keywords><keyword>Animals</keyword><keyword>Cytokines/immunology/metabolism</keyword><keyword>Homeostasis/immunology</keyword><keyword>Humans</keyword><keyword>Inflammation Mediators/immunology/metabolism</keyword><keyword>Insulin Resistance/*immunology</keyword><keyword>Macrophage Activation/*immunology</keyword><keyword>Macrophages/*immunology</keyword><keyword>Models, Immunological</keyword><keyword>Obesity/*immunology/metabolism</keyword></keywords><dates><year>2011</year><pub-dates><date>Oct 10</date></pub-dates></dates><isbn>1474-1741 (Electronic) 1474-1733 (Linking)</isbn><accession-num>21984069</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21984069</url></related-urls></urls><custom2>3383854</custom2><electronic-resource-num>10.1038/nri3071</electronic-resource-num></record></Cite></EndNote>184. The expression of TLR-4 is elevated in skeletal muscle 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ADDIN EN.CITE.DATA 185 and adipose tissue 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ADDIN EN.CITE.DATA 148 with obesity. Thus, mice with reduced TLR-2- or TLR-4-signalling proteins <EndNote><Cite><Author>Shi</Author><Year>2006</Year><RecNum>413</RecNum><DisplayText>[148, 186, 187]</DisplayText><record><rec-number>413</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">413</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shi, H.</author><author>Kokoeva, M. V.</author><author>Inouye, K.</author><author>Tzameli, I.</author><author>Yin, H.</author><author>Flier, J. S.</author></authors></contributors><auth-address>Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA.</auth-address><titles><title>TLR4 links innate immunity and fatty acid-induced insulin resistance</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>3015-25</pages><volume>116</volume><number>11</number><keywords><keyword>Adipocytes/drug effects/metabolism</keyword><keyword>Adipose Tissue/drug effects/metabolism</keyword><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Cytokines/genetics/metabolism</keyword><keyword>Fats/pharmacology</keyword><keyword>Fatty Acids/*pharmacology</keyword><keyword>Female</keyword><keyword>Genes, Reporter/genetics</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Immunity, Innate/*immunology</keyword><keyword>*Insulin Resistance</keyword><keyword>Macrophages/drug effects/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Muscles/drug effects/metabolism</keyword><keyword>NF-kappa B/metabolism</keyword><keyword>Signal Transduction/drug effects</keyword><keyword>Toll-Like Receptor 4/deficiency/genetics/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>17053832</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17053832</url></related-urls></urls><custom2>1616196</custom2><electronic-resource-num>10.1172/JCI28898</electronic-resource-num></record></Cite><Cite><Author>Kleinridders</Author><Year>2009</Year><RecNum>444</RecNum><record><rec-number>444</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">444</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kleinridders, A.</author><author>Schenten, D.</author><author>Konner, A. C.</author><author>Belgardt, B. F.</author><author>Mauer, J.</author><author>Okamura, T.</author><author>Wunderlich, F. T.</author><author>Medzhitov, R.</author><author>Bruning, J. C.</author></authors></contributors><auth-address>Department of Mouse Genetics and Metabolism, Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, D-50674 Cologne, Germany.</auth-address><titles><title>MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity</title><secondary-title>Cell Metab</secondary-title><alt-title>Cell metabolism</alt-title></titles><periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></periodical><alt-periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></alt-periodical><pages>249-59</pages><volume>10</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Central Nervous System/*metabolism</keyword><keyword>*Diet</keyword><keyword>Dietary Fats/metabolism</keyword><keyword>Eating</keyword><keyword>Energy Metabolism</keyword><keyword>Enzyme Activation</keyword><keyword>Female</keyword><keyword>Glucose/metabolism</keyword><keyword>Homeostasis</keyword><keyword>Humans</keyword><keyword>I-kappa B Kinase/metabolism</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance</keyword><keyword>Leptin/*metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Transgenic</keyword><keyword>Motor Activity/physiology</keyword><keyword>Myeloid Differentiation Factor 88/genetics/*metabolism</keyword><keyword>Obesity/*metabolism</keyword><keyword>Palmitic Acid/*metabolism</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Weight Gain</keyword></keywords><dates><year>2009</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1932-7420 (Electronic)&#xD;1550-4131 (Linking)</isbn><accession-num>19808018</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19808018</url></related-urls></urls><custom2>3898351</custom2><electronic-resource-num>10.1016/j.cmet.2009.08.013</electronic-resource-num></record></Cite><Cite><Author>Himes</Author><Year>2010</Year><RecNum>445</RecNum><record><rec-number>445</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">445</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Himes, R. W.</author><author>Smith, C. W.</author></authors></contributors><auth-address>Texas Children&apos;s Hospital, Section of Pediatric Gastroenterology, 1102 Bates St., Texas Children&apos;s Feigin Center, Rm. 860B, Houston, TX, 77030, USA. himes@bcm.tmc.edu</auth-address><titles><title>Tlr2 is critical for diet-induced metabolic syndrome in a murine model</title><secondary-title>FASEB J</secondary-title><alt-title>FASEB journal : official publication of the Federation of American Societies for Experimental Biology</alt-title></titles><periodical><full-title>FASEB J</full-title><abbr-1>FASEB journal : official publication of the Federation of American Societies for Experimental Biology</abbr-1></periodical><alt-periodical><full-title>FASEB J</full-title><abbr-1>FASEB journal : official publication of the Federation of American Societies for Experimental Biology</abbr-1></alt-periodical><pages>731-9</pages><volume>24</volume><number>3</number><keywords><keyword>Absorptiometry, Photon</keyword><keyword>Adipose Tissue/metabolism/pathology</keyword><keyword>Animals</keyword><keyword>Body Composition/genetics/physiology</keyword><keyword>Calorimetry</keyword><keyword>Fatty Liver/genetics/pathology</keyword><keyword>Glucose/metabolism</keyword><keyword>Insulin Resistance/genetics/physiology</keyword><keyword>Lipids/blood</keyword><keyword>Lipoproteins, VLDL/blood</keyword><keyword>Liver/metabolism/pathology</keyword><keyword>Male</keyword><keyword>Metabolic Syndrome/blood/chemically induced/*genetics</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Mutant Strains</keyword><keyword>Obesity/genetics/physiopathology</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Toll-Like Receptor 2/genetics/*physiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1530-6860 (Electronic)&#xD;0892-6638 (Linking)</isbn><accession-num>19841034</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19841034</url></related-urls></urls><custom2>2830137</custom2><electronic-resource-num>10.1096/fj.09-141929</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Shi</Author><Year>2006</Year><RecNum>413</RecNum><DisplayText>[148, 186, 187]</DisplayText><record><rec-number>413</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">413</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shi, H.</author><author>Kokoeva, M. V.</author><author>Inouye, K.</author><author>Tzameli, I.</author><author>Yin, H.</author><author>Flier, J. S.</author></authors></contributors><auth-address>Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA.</auth-address><titles><title>TLR4 links innate immunity and fatty acid-induced insulin resistance</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>3015-25</pages><volume>116</volume><number>11</number><keywords><keyword>Adipocytes/drug effects/metabolism</keyword><keyword>Adipose Tissue/drug effects/metabolism</keyword><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Cytokines/genetics/metabolism</keyword><keyword>Fats/pharmacology</keyword><keyword>Fatty Acids/*pharmacology</keyword><keyword>Female</keyword><keyword>Genes, Reporter/genetics</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Immunity, Innate/*immunology</keyword><keyword>*Insulin Resistance</keyword><keyword>Macrophages/drug effects/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Muscles/drug effects/metabolism</keyword><keyword>NF-kappa B/metabolism</keyword><keyword>Signal Transduction/drug effects</keyword><keyword>Toll-Like Receptor 4/deficiency/genetics/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0021-9738 (Print)&#xD;0021-9738 (Linking)</isbn><accession-num>17053832</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17053832</url></related-urls></urls><custom2>1616196</custom2><electronic-resource-num>10.1172/JCI28898</electronic-resource-num></record></Cite><Cite><Author>Kleinridders</Author><Year>2009</Year><RecNum>444</RecNum><record><rec-number>444</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">444</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kleinridders, A.</author><author>Schenten, D.</author><author>Konner, A. C.</author><author>Belgardt, B. F.</author><author>Mauer, J.</author><author>Okamura, T.</author><author>Wunderlich, F. T.</author><author>Medzhitov, R.</author><author>Bruning, J. C.</author></authors></contributors><auth-address>Department of Mouse Genetics and Metabolism, Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, D-50674 Cologne, Germany.</auth-address><titles><title>MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity</title><secondary-title>Cell Metab</secondary-title><alt-title>Cell metabolism</alt-title></titles><periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></periodical><alt-periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></alt-periodical><pages>249-59</pages><volume>10</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Central Nervous System/*metabolism</keyword><keyword>*Diet</keyword><keyword>Dietary Fats/metabolism</keyword><keyword>Eating</keyword><keyword>Energy Metabolism</keyword><keyword>Enzyme Activation</keyword><keyword>Female</keyword><keyword>Glucose/metabolism</keyword><keyword>Homeostasis</keyword><keyword>Humans</keyword><keyword>I-kappa B Kinase/metabolism</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance</keyword><keyword>Leptin/*metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Transgenic</keyword><keyword>Motor Activity/physiology</keyword><keyword>Myeloid Differentiation Factor 88/genetics/*metabolism</keyword><keyword>Obesity/*metabolism</keyword><keyword>Palmitic Acid/*metabolism</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Weight Gain</keyword></keywords><dates><year>2009</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1932-7420 (Electronic)&#xD;1550-4131 (Linking)</isbn><accession-num>19808018</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19808018</url></related-urls></urls><custom2>3898351</custom2><electronic-resource-num>10.1016/j.cmet.2009.08.013</electronic-resource-num></record></Cite><Cite><Author>Himes</Author><Year>2010</Year><RecNum>445</RecNum><record><rec-number>445</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">445</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Himes, R. W.</author><author>Smith, C. W.</author></authors></contributors><auth-address>Texas Children&apos;s Hospital, Section of Pediatric Gastroenterology, 1102 Bates St., Texas Children&apos;s Feigin Center, Rm. 860B, Houston, TX, 77030, USA. himes@bcm.tmc.edu</auth-address><titles><title>Tlr2 is critical for diet-induced metabolic syndrome in a murine model</title><secondary-title>FASEB J</secondary-title><alt-title>FASEB journal : official publication of the Federation of American Societies for Experimental Biology</alt-title></titles><periodical><full-title>FASEB J</full-title><abbr-1>FASEB journal : official publication of the Federation of American Societies for Experimental Biology</abbr-1></periodical><alt-periodical><full-title>FASEB J</full-title><abbr-1>FASEB journal : official publication of the Federation of American Societies for Experimental Biology</abbr-1></alt-periodical><pages>731-9</pages><volume>24</volume><number>3</number><keywords><keyword>Absorptiometry, Photon</keyword><keyword>Adipose Tissue/metabolism/pathology</keyword><keyword>Animals</keyword><keyword>Body Composition/genetics/physiology</keyword><keyword>Calorimetry</keyword><keyword>Fatty Liver/genetics/pathology</keyword><keyword>Glucose/metabolism</keyword><keyword>Insulin Resistance/genetics/physiology</keyword><keyword>Lipids/blood</keyword><keyword>Lipoproteins, VLDL/blood</keyword><keyword>Liver/metabolism/pathology</keyword><keyword>Male</keyword><keyword>Metabolic Syndrome/blood/chemically induced/*genetics</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Mutant Strains</keyword><keyword>Obesity/genetics/physiopathology</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Toll-Like Receptor 2/genetics/*physiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1530-6860 (Electronic)&#xD;0892-6638 (Linking)</isbn><accession-num>19841034</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19841034</url></related-urls></urls><custom2>2830137</custom2><electronic-resource-num>10.1096/fj.09-141929</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 148, 186, 187 are protected from obesity and obesity-associated IR.1.4.3.c.Hyperglycemia:Sustained hyperglycemia can alter insulin sensitivity in muscle and adipose tissue, as well as decreased insulin secretion from ? cells 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 188, 189. Impaired glucose uptake in skeletal muscle can also hamper insulin action in adipose tissue and liver due to glucose toxicity 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 190, 191. Thus, chronic hyperglycemia leading to insulin resistance (IR) is the primary etiological factor in the pathogenesis of diabetic microvascular disease and is implicated in macrovascular complications 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ADDIN EN.CITE.DATA 192, 193. One possible mechanism of hyperglycemia-induced tissue damage in diabetes is the formation of advanced glycation end products (AGEs). Under chronic hyperglycemia state, a non-enzymatic glycation between reducing glucose and free amino groups of proteins, resulting in the irreversible formation of AGEs ADDIN EN.CITE <EndNote><Cite><Author>Vlassara</Author><Year>2002</Year><RecNum>330</RecNum><DisplayText>194</DisplayText><record><rec-number>330</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>330</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Vlassara, H.</author><author>Palace, M. R.</author></authors></contributors><auth-address>Department of Geriatrics, Mount Sinai School of Medicine, NY 10029, USA. [email protected]</auth-address><titles><title>Diabetes and advanced glycation endproducts</title><secondary-title>J Intern Med</secondary-title><alt-title>Journal of internal medicine</alt-title></titles><periodical><full-title>J Intern Med</full-title><abbr-1>Journal of internal medicine</abbr-1></periodical><alt-periodical><full-title>J Intern Med</full-title><abbr-1>Journal of internal medicine</abbr-1></alt-periodical><pages>87-101</pages><volume>251</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus/pathology/*physiopathology</keyword><keyword>Diabetes Mellitus, Experimental/pathology/physiopathology</keyword><keyword>Diabetic Angiopathies/pathology/physiopathology</keyword><keyword>Diabetic Nephropathies/pathology/physiopathology</keyword><keyword>Disease Progression</keyword><keyword>Endothelium, Vascular/pathology</keyword><keyword>Glycation End Products, Advanced/*physiology</keyword><keyword>Humans</keyword><keyword>Kidney Glomerulus/pathology</keyword><keyword>Receptor for Advanced Glycation End Products</keyword><keyword>Receptors, Immunologic/physiology</keyword></keywords><dates><year>2002</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0954-6820 (Print) 0954-6820 (Linking)</isbn><accession-num>11905595</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11905595</url></related-urls></urls></record></Cite></EndNote>194 which inhibit insulin signalling by increasing Ser-307 phosphorylation of IRS-1 and forming methylglyoxal-IRS-1 adducts 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 195. Hyperglycemia increases the flux through the polyol pathway that leads to O-GlcNAcylation of IR, which impairs receptor dimerization 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 196 and IRS proteins, which causes JNK activation and increases the hexosamine-biosynthetic pathway to promote IR in adipose tissue, skeletal muscle, liver, and pancreas <EndNote><Cite><Author>Marshall</Author><Year>1991</Year><RecNum>452</RecNum><DisplayText>[197-200]</DisplayText><record><rec-number>452</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">452</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Marshall, S.</author><author>Bacote, V.</author><author>Traxinger, R. R.</author></authors></contributors><auth-address>Department of Biochemistry, University of Tennessee, Memphis 38163.</auth-address><titles><title>Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>4706-12</pages><volume>266</volume><number>8</number><keywords><keyword>Animals</keyword><keyword>Azaserine/pharmacology</keyword><keyword>Biological Transport</keyword><keyword>Glucosamine/metabolism</keyword><keyword>Glucose/*metabolism</keyword><keyword>Glutamine/metabolism</keyword><keyword>Hexosamines/*biosynthesis</keyword><keyword>*Insulin Resistance</keyword><keyword>Male</keyword><keyword>Rats</keyword><keyword>Rats, Inbred Strains</keyword></keywords><dates><year>1991</year><pub-dates><date>Mar 15</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>2002019</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/2002019</url></related-urls></urls></record></Cite><Cite><Author>Patti</Author><Year>1999</Year><RecNum>453</RecNum><record><rec-number>453</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">453</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Patti, M. E.</author><author>Virkamaki, A.</author><author>Landaker, E. J.</author><author>Kahn, C. R.</author><author>Yki-Jarvinen, H.</author></authors></contributors><auth-address>Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA. pattim@joslab.harvard.edu</auth-address><titles><title>Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>1562-71</pages><volume>48</volume><number>8</number><keywords><keyword>Animals</keyword><keyword>Enzyme Activation/physiology</keyword><keyword>Glucosamine/*physiology</keyword><keyword>Glycosylation</keyword><keyword>Hexosamines/*metabolism</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Lipid Metabolism</keyword><keyword>Male</keyword><keyword>Muscle, Skeletal/enzymology/*metabolism</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Phosphotransferases/metabolism</keyword><keyword>Protein Isoforms/metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Receptor, Insulin/metabolism/*physiology</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>1999</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>10426374</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10426374</url></related-urls></urls></record></Cite><Cite><Author>McClain</Author><Year>2002</Year><RecNum>454</RecNum><record><rec-number>454</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">454</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McClain, D. A.</author></authors></contributors><auth-address>Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Utah and VA Medical Center, 50 N. Medical Drive, 4C116, Salt Lake City, UT 84132, USA. donald.mcclain@hsc.utah.edu</auth-address><titles><title>Hexosamines as mediators of nutrient sensing and regulation in diabetes</title><secondary-title>J Diabetes Complications</secondary-title><alt-title>Journal of diabetes and its complications</alt-title></titles><periodical><full-title>J Diabetes Complications</full-title><abbr-1>Journal of diabetes and its complications</abbr-1></periodical><alt-periodical><full-title>J Diabetes Complications</full-title><abbr-1>Journal of diabetes and its complications</abbr-1></alt-periodical><pages>72-80</pages><volume>16</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus/*physiopathology</keyword><keyword>Dietary Fats</keyword><keyword>Fatty Acids, Nonesterified/blood</keyword><keyword>Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/genetics/metabolism</keyword><keyword>Hexosamines/*physiology</keyword><keyword>Humans</keyword><keyword>Insulin/secretion</keyword><keyword>Islets of Langerhans/secretion</keyword><keyword>Liver/enzymology</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>2002</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>1056-8727 (Print)&#xD;1056-8727 (Linking)</isbn><accession-num>11872372</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11872372</url></related-urls></urls></record></Cite><Cite><Author>McClain</Author><Year>2002</Year><RecNum>455</RecNum><record><rec-number>455</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">455</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McClain, D. A.</author><author>Lubas, W. A.</author><author>Cooksey, R. C.</author><author>Hazel, M.</author><author>Parker, G. J.</author><author>Love, D. C.</author><author>Hanover, J. A.</author></authors></contributors><auth-address>Department of Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT 84112, USA.</auth-address><titles><title>Altered glycan-dependent signaling induces insulin resistance and hyperleptinemia</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>10695-9</pages><volume>99</volume><number>16</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Diabetes Mellitus, Type 2/blood/*enzymology</keyword><keyword>Disease Models, Animal</keyword><keyword>Female</keyword><keyword>Gene Expression</keyword><keyword>Glucose Transporter Type 4</keyword><keyword>Humans</keyword><keyword>Insulin/blood</keyword><keyword>*Insulin Resistance</keyword><keyword>Leptin/*blood/genetics</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Monosaccharide Transport Proteins/genetics</keyword><keyword>*Muscle Proteins</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>N-Acetylglucosaminyltransferases/genetics/*metabolism/physiology</keyword><keyword>Polysaccharides/metabolism</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>Recombinant Fusion Proteins/genetics</keyword><keyword>*Signal Transduction</keyword><keyword>*Up-Regulation</keyword><keyword>Uridine Diphosphate N-Acetylglucosamine/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug 6</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>12136128</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12136128</url></related-urls></urls><custom2>125016</custom2><electronic-resource-num>10.1073/pnas.152346899</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Marshall</Author><Year>1991</Year><RecNum>452</RecNum><DisplayText>[197-200]</DisplayText><record><rec-number>452</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">452</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Marshall, S.</author><author>Bacote, V.</author><author>Traxinger, R. R.</author></authors></contributors><auth-address>Department of Biochemistry, University of Tennessee, Memphis 38163.</auth-address><titles><title>Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>4706-12</pages><volume>266</volume><number>8</number><keywords><keyword>Animals</keyword><keyword>Azaserine/pharmacology</keyword><keyword>Biological Transport</keyword><keyword>Glucosamine/metabolism</keyword><keyword>Glucose/*metabolism</keyword><keyword>Glutamine/metabolism</keyword><keyword>Hexosamines/*biosynthesis</keyword><keyword>*Insulin Resistance</keyword><keyword>Male</keyword><keyword>Rats</keyword><keyword>Rats, Inbred Strains</keyword></keywords><dates><year>1991</year><pub-dates><date>Mar 15</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>2002019</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/2002019</url></related-urls></urls></record></Cite><Cite><Author>Patti</Author><Year>1999</Year><RecNum>453</RecNum><record><rec-number>453</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">453</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Patti, M. E.</author><author>Virkamaki, A.</author><author>Landaker, E. J.</author><author>Kahn, C. R.</author><author>Yki-Jarvinen, H.</author></authors></contributors><auth-address>Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA. pattim@joslab.harvard.edu</auth-address><titles><title>Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>1562-71</pages><volume>48</volume><number>8</number><keywords><keyword>Animals</keyword><keyword>Enzyme Activation/physiology</keyword><keyword>Glucosamine/*physiology</keyword><keyword>Glycosylation</keyword><keyword>Hexosamines/*metabolism</keyword><keyword>Insulin/*physiology</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Lipid Metabolism</keyword><keyword>Male</keyword><keyword>Muscle, Skeletal/enzymology/*metabolism</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Phosphotransferases/metabolism</keyword><keyword>Protein Isoforms/metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Receptor, Insulin/metabolism/*physiology</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Tyrosine/metabolism</keyword></keywords><dates><year>1999</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>10426374</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10426374</url></related-urls></urls></record></Cite><Cite><Author>McClain</Author><Year>2002</Year><RecNum>454</RecNum><record><rec-number>454</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">454</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McClain, D. A.</author></authors></contributors><auth-address>Department of Internal Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Utah and VA Medical Center, 50 N. Medical Drive, 4C116, Salt Lake City, UT 84132, USA. donald.mcclain@hsc.utah.edu</auth-address><titles><title>Hexosamines as mediators of nutrient sensing and regulation in diabetes</title><secondary-title>J Diabetes Complications</secondary-title><alt-title>Journal of diabetes and its complications</alt-title></titles><periodical><full-title>J Diabetes Complications</full-title><abbr-1>Journal of diabetes and its complications</abbr-1></periodical><alt-periodical><full-title>J Diabetes Complications</full-title><abbr-1>Journal of diabetes and its complications</abbr-1></alt-periodical><pages>72-80</pages><volume>16</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus/*physiopathology</keyword><keyword>Dietary Fats</keyword><keyword>Fatty Acids, Nonesterified/blood</keyword><keyword>Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/genetics/metabolism</keyword><keyword>Hexosamines/*physiology</keyword><keyword>Humans</keyword><keyword>Insulin/secretion</keyword><keyword>Islets of Langerhans/secretion</keyword><keyword>Liver/enzymology</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Triglycerides/blood</keyword></keywords><dates><year>2002</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>1056-8727 (Print)&#xD;1056-8727 (Linking)</isbn><accession-num>11872372</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11872372</url></related-urls></urls></record></Cite><Cite><Author>McClain</Author><Year>2002</Year><RecNum>455</RecNum><record><rec-number>455</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">455</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McClain, D. 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A.</author></authors></contributors><auth-address>Department of Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT 84112, USA.</auth-address><titles><title>Altered glycan-dependent signaling induces insulin resistance and hyperleptinemia</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>10695-9</pages><volume>99</volume><number>16</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Diabetes Mellitus, Type 2/blood/*enzymology</keyword><keyword>Disease Models, Animal</keyword><keyword>Female</keyword><keyword>Gene Expression</keyword><keyword>Glucose Transporter Type 4</keyword><keyword>Humans</keyword><keyword>Insulin/blood</keyword><keyword>*Insulin Resistance</keyword><keyword>Leptin/*blood/genetics</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Monosaccharide Transport Proteins/genetics</keyword><keyword>*Muscle Proteins</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>N-Acetylglucosaminyltransferases/genetics/*metabolism/physiology</keyword><keyword>Polysaccharides/metabolism</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>Recombinant Fusion Proteins/genetics</keyword><keyword>*Signal Transduction</keyword><keyword>*Up-Regulation</keyword><keyword>Uridine Diphosphate N-Acetylglucosamine/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Aug 6</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>12136128</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12136128</url></related-urls></urls><custom2>125016</custom2><electronic-resource-num>10.1073/pnas.152346899</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 197-200. Furthermore, hyperglycemia forms a multimolecular complex, including receptor AGE/IRS-1/Src that induces IRS-1 Ser-307 phosphorylation via activation of PKC-? 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 201, 202.1.4.3.d.Mitochondrial Dysfunction and ROS Formation:Mitochondrial dysfunction is a collective term attributed to multiple abnormalities of mitochondria such as a reduction in mitochondrial content and mitochondrial biogenesis, and/or a decrease in the expression of mitochondrial oxidative proteins. A diminished electron flow through the electron transport chain can subsequently cause electron leakage and superoxide generation, followed by oxidative stress and damage. Increased ROS levels in obese and diabetic patients enhance metabolic flux into the mitochondria, alters mitochondrial proteins and reduced expression of antioxidant enzymes <EndNote><Cite><Author>West</Author><Year>2000</Year><RecNum>458</RecNum><DisplayText>[203-206]</DisplayText><record><rec-number>458</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">458</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>West, I. C.</author></authors></contributors><auth-address>Department of Biochemistry and Genetics, University of Newcastle upon Tyne, UK. i.c.west@ncl.ac.uk</auth-address><titles><title>Radicals and oxidative stress in diabetes</title><secondary-title>Diabet Med</secondary-title><alt-title>Diabetic medicine : a journal of the British Diabetic Association</alt-title></titles><periodical><full-title>Diabet Med</full-title><abbr-1>Diabetic medicine : a journal of the British Diabetic Association</abbr-1></periodical><alt-periodical><full-title>Diabet Med</full-title><abbr-1>Diabetic medicine : a journal of the British Diabetic Association</abbr-1></alt-periodical><pages>171-80</pages><volume>17</volume><number>3</number><keywords><keyword>*Diabetes Mellitus, Type 1/etiology/physiopathology</keyword><keyword>*Diabetes Mellitus, Type 2/etiology/genetics/physiopathology</keyword><keyword>Free Radicals</keyword><keyword>Humans</keyword><keyword>Hyperglycemia/complications</keyword><keyword>*Oxidative Stress</keyword><keyword>Reactive Oxygen Species</keyword></keywords><dates><year>2000</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0742-3071 (Print)&#xD;0742-3071 (Linking)</isbn><accession-num>10784220</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10784220</url></related-urls></urls></record></Cite><Cite><Author>Rosen</Author><Year>2001</Year><RecNum>459</RecNum><record><rec-number>459</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">459</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rosen, P.</author><author>Nawroth, P. P.</author><author>King, G.</author><author>Moller, W.</author><author>Tritschler, H. J.</author><author>Packer, L.</author></authors></contributors><auth-address>Deutsches Diabetesforschungsinstitut, Dusseldorf, Germany. roesen@uni-duesseldorf.de</auth-address><titles><title>The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society</title><secondary-title>Diabetes Metab Res Rev</secondary-title><alt-title>Diabetes/metabolism research and reviews</alt-title></titles><periodical><full-title>Diabetes Metab Res Rev</full-title><abbr-1>Diabetes/metabolism research and reviews</abbr-1></periodical><alt-periodical><full-title>Diabetes Metab Res Rev</full-title><abbr-1>Diabetes/metabolism research and reviews</abbr-1></alt-periodical><pages>189-212</pages><volume>17</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Cardiovascular Diseases/physiopathology</keyword><keyword>Congresses as Topic</keyword><keyword>Diabetes Complications</keyword><keyword>Diabetes Mellitus/*physiopathology</keyword><keyword>Diabetic Angiopathies/physiopathology</keyword><keyword>Diabetic Neuropathies/physiopathology</keyword><keyword>Disease Progression</keyword><keyword>Glycation End Products, Advanced/physiology</keyword><keyword>Humans</keyword><keyword>*Oxidative Stress</keyword><keyword>Reactive Oxygen Species/physiology</keyword><keyword>Transcription Factors/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>May-Jun</date></pub-dates></dates><isbn>1520-7552 (Print)&#xD;1520-7552 (Linking)</isbn><accession-num>11424232</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11424232</url></related-urls></urls></record></Cite><Cite><Author>Evans</Author><Year>2005</Year><RecNum>460</RecNum><record><rec-number>460</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">460</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Evans, J. L.</author><author>Maddux, B. A.</author><author>Goldfine, I. D.</author></authors></contributors><auth-address>Medical Research Institute, San Francisco, CA 94107, USA. jevansphd@earthlink.net</auth-address><titles><title>The molecular basis for oxidative stress-induced insulin resistance</title><secondary-title>Antioxid Redox Signal</secondary-title><alt-title>Antioxidants &amp; redox signaling</alt-title></titles><periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></periodical><alt-periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></alt-periodical><pages>1040-52</pages><volume>7</volume><number>7-8</number><keywords><keyword>Animals</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Oxidation-Reduction</keyword><keyword>*Oxidative Stress</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>1523-0864 (Print)&#xD;1523-0864 (Linking)</isbn><accession-num>15998259</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15998259</url></related-urls></urls><electronic-resource-num>10.1089/ars.2005.7.1040</electronic-resource-num></record></Cite><Cite><Author>Fridlyand</Author><Year>2006</Year><RecNum>461</RecNum><record><rec-number>461</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">461</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fridlyand, L. E.</author><author>Philipson, L. H.</author></authors></contributors><auth-address>Department of Medicine, University of Chicago, Chicago, IL 60637, USA.</auth-address><titles><title>Reactive species and early manifestation of insulin resistance in type 2 diabetes</title><secondary-title>Diabetes Obes Metab</secondary-title><alt-title>Diabetes, obesity &amp; metabolism</alt-title></titles><periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></periodical><alt-periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></alt-periodical><pages>136-45</pages><volume>8</volume><number>2</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/physiology</keyword><keyword>Lipid Metabolism</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Oxidative Stress/physiology</keyword><keyword>Reactive Oxygen Species/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1462-8902 (Print)&#xD;1462-8902 (Linking)</isbn><accession-num>16448517</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16448517</url></related-urls></urls><electronic-resource-num>10.1111/j.1463-1326.2005.00496.x</electronic-resource-num></record></Cite><Cite><Author>Fridlyand</Author><Year>2006</Year><RecNum>461</RecNum><record><rec-number>461</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">461</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fridlyand, L. E.</author><author>Philipson, L. H.</author></authors></contributors><auth-address>Department of Medicine, University of Chicago, Chicago, IL 60637, USA.</auth-address><titles><title>Reactive species and early manifestation of insulin resistance in type 2 diabetes</title><secondary-title>Diabetes Obes Metab</secondary-title><alt-title>Diabetes, obesity &amp; metabolism</alt-title></titles><periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></periodical><alt-periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></alt-periodical><pages>136-45</pages><volume>8</volume><number>2</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/physiology</keyword><keyword>Lipid Metabolism</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Oxidative Stress/physiology</keyword><keyword>Reactive Oxygen Species/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1462-8902 (Print)&#xD;1462-8902 (Linking)</isbn><accession-num>16448517</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16448517</url></related-urls></urls><electronic-resource-num>10.1111/j.1463-1326.2005.00496.x</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>West</Author><Year>2000</Year><RecNum>458</RecNum><DisplayText>[203-206]</DisplayText><record><rec-number>458</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">458</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>West, I. C.</author></authors></contributors><auth-address>Department of Biochemistry and Genetics, University of Newcastle upon Tyne, UK. i.c.west@ncl.ac.uk</auth-address><titles><title>Radicals and oxidative stress in diabetes</title><secondary-title>Diabet Med</secondary-title><alt-title>Diabetic medicine : a journal of the British Diabetic Association</alt-title></titles><periodical><full-title>Diabet Med</full-title><abbr-1>Diabetic medicine : a journal of the British Diabetic Association</abbr-1></periodical><alt-periodical><full-title>Diabet Med</full-title><abbr-1>Diabetic medicine : a journal of the British Diabetic Association</abbr-1></alt-periodical><pages>171-80</pages><volume>17</volume><number>3</number><keywords><keyword>*Diabetes Mellitus, Type 1/etiology/physiopathology</keyword><keyword>*Diabetes Mellitus, Type 2/etiology/genetics/physiopathology</keyword><keyword>Free Radicals</keyword><keyword>Humans</keyword><keyword>Hyperglycemia/complications</keyword><keyword>*Oxidative Stress</keyword><keyword>Reactive Oxygen Species</keyword></keywords><dates><year>2000</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0742-3071 (Print)&#xD;0742-3071 (Linking)</isbn><accession-num>10784220</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10784220</url></related-urls></urls></record></Cite><Cite><Author>Rosen</Author><Year>2001</Year><RecNum>459</RecNum><record><rec-number>459</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">459</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rosen, P.</author><author>Nawroth, P. P.</author><author>King, G.</author><author>Moller, W.</author><author>Tritschler, H. J.</author><author>Packer, L.</author></authors></contributors><auth-address>Deutsches Diabetesforschungsinstitut, Dusseldorf, Germany. roesen@uni-duesseldorf.de</auth-address><titles><title>The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society</title><secondary-title>Diabetes Metab Res Rev</secondary-title><alt-title>Diabetes/metabolism research and reviews</alt-title></titles><periodical><full-title>Diabetes Metab Res Rev</full-title><abbr-1>Diabetes/metabolism research and reviews</abbr-1></periodical><alt-periodical><full-title>Diabetes Metab Res Rev</full-title><abbr-1>Diabetes/metabolism research and reviews</abbr-1></alt-periodical><pages>189-212</pages><volume>17</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Cardiovascular Diseases/physiopathology</keyword><keyword>Congresses as Topic</keyword><keyword>Diabetes Complications</keyword><keyword>Diabetes Mellitus/*physiopathology</keyword><keyword>Diabetic Angiopathies/physiopathology</keyword><keyword>Diabetic Neuropathies/physiopathology</keyword><keyword>Disease Progression</keyword><keyword>Glycation End Products, Advanced/physiology</keyword><keyword>Humans</keyword><keyword>*Oxidative Stress</keyword><keyword>Reactive Oxygen Species/physiology</keyword><keyword>Transcription Factors/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>May-Jun</date></pub-dates></dates><isbn>1520-7552 (Print)&#xD;1520-7552 (Linking)</isbn><accession-num>11424232</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11424232</url></related-urls></urls></record></Cite><Cite><Author>Evans</Author><Year>2005</Year><RecNum>460</RecNum><record><rec-number>460</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">460</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Evans, J. L.</author><author>Maddux, B. A.</author><author>Goldfine, I. D.</author></authors></contributors><auth-address>Medical Research Institute, San Francisco, CA 94107, USA. jevansphd@earthlink.net</auth-address><titles><title>The molecular basis for oxidative stress-induced insulin resistance</title><secondary-title>Antioxid Redox Signal</secondary-title><alt-title>Antioxidants &amp; redox signaling</alt-title></titles><periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></periodical><alt-periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></alt-periodical><pages>1040-52</pages><volume>7</volume><number>7-8</number><keywords><keyword>Animals</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Oxidation-Reduction</keyword><keyword>*Oxidative Stress</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>1523-0864 (Print)&#xD;1523-0864 (Linking)</isbn><accession-num>15998259</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15998259</url></related-urls></urls><electronic-resource-num>10.1089/ars.2005.7.1040</electronic-resource-num></record></Cite><Cite><Author>Fridlyand</Author><Year>2006</Year><RecNum>461</RecNum><record><rec-number>461</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">461</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fridlyand, L. E.</author><author>Philipson, L. H.</author></authors></contributors><auth-address>Department of Medicine, University of Chicago, Chicago, IL 60637, USA.</auth-address><titles><title>Reactive species and early manifestation of insulin resistance in type 2 diabetes</title><secondary-title>Diabetes Obes Metab</secondary-title><alt-title>Diabetes, obesity &amp; metabolism</alt-title></titles><periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></periodical><alt-periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></alt-periodical><pages>136-45</pages><volume>8</volume><number>2</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/physiology</keyword><keyword>Lipid Metabolism</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Oxidative Stress/physiology</keyword><keyword>Reactive Oxygen Species/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1462-8902 (Print)&#xD;1462-8902 (Linking)</isbn><accession-num>16448517</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16448517</url></related-urls></urls><electronic-resource-num>10.1111/j.1463-1326.2005.00496.x</electronic-resource-num></record></Cite><Cite><Author>Fridlyand</Author><Year>2006</Year><RecNum>461</RecNum><record><rec-number>461</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">461</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fridlyand, L. E.</author><author>Philipson, L. H.</author></authors></contributors><auth-address>Department of Medicine, University of Chicago, Chicago, IL 60637, USA.</auth-address><titles><title>Reactive species and early manifestation of insulin resistance in type 2 diabetes</title><secondary-title>Diabetes Obes Metab</secondary-title><alt-title>Diabetes, obesity &amp; metabolism</alt-title></titles><periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></periodical><alt-periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></alt-periodical><pages>136-45</pages><volume>8</volume><number>2</number><keywords><keyword>Adipocytes/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/physiology</keyword><keyword>Lipid Metabolism</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Oxidative Stress/physiology</keyword><keyword>Reactive Oxygen Species/*metabolism</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1462-8902 (Print)&#xD;1462-8902 (Linking)</isbn><accession-num>16448517</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16448517</url></related-urls></urls><electronic-resource-num>10.1111/j.1463-1326.2005.00496.x</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 203-206. Augmented oxidative stress leads to the activation of stress kinases that induce IR by serine phosphorylation of IRS proteins <EndNote><Cite><Author>Rudich</Author><Year>1998</Year><RecNum>462</RecNum><DisplayText>[205, 207, 208]</DisplayText><record><rec-number>462</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">462</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rudich, A.</author><author>Tirosh, A.</author><author>Potashnik, R.</author><author>Hemi, R.</author><author>Kanety, H.</author><author>Bashan, N.</author></authors></contributors><auth-address>Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.</auth-address><titles><title>Prolonged oxidative stress impairs insulin-induced GLUT4 translocation in 3T3-L1 adipocytes</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>1562-9</pages><volume>47</volume><number>10</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/*drug effects/*metabolism/ultrastructure</keyword><keyword>Animals</keyword><keyword>Biological Transport</keyword><keyword>Cell Membrane/metabolism</keyword><keyword>Deoxyglucose/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Glucose Transporter Type 1</keyword><keyword>Glucose Transporter Type 4</keyword><keyword>Hydrogen Peroxide/pharmacology</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Mice</keyword><keyword>Microsomes/enzymology</keyword><keyword>Monosaccharide Transport Proteins/*metabolism</keyword><keyword>*Muscle Proteins</keyword><keyword>Osmolar Concentration</keyword><keyword>*Oxidative Stress</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword></keywords><dates><year>1998</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>9753293</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9753293</url></related-urls></urls></record></Cite><Cite><Author>Evans</Author><Year>2005</Year><RecNum>460</RecNum><record><rec-number>460</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">460</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Evans, J. L.</author><author>Maddux, B. A.</author><author>Goldfine, I. D.</author></authors></contributors><auth-address>Medical Research Institute, San Francisco, CA 94107, USA. jevansphd@earthlink.net</auth-address><titles><title>The molecular basis for oxidative stress-induced insulin resistance</title><secondary-title>Antioxid Redox Signal</secondary-title><alt-title>Antioxidants &amp; redox signaling</alt-title></titles><periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></periodical><alt-periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></alt-periodical><pages>1040-52</pages><volume>7</volume><number>7-8</number><keywords><keyword>Animals</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Oxidation-Reduction</keyword><keyword>*Oxidative Stress</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>1523-0864 (Print)&#xD;1523-0864 (Linking)</isbn><accession-num>15998259</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15998259</url></related-urls></urls><electronic-resource-num>10.1089/ars.2005.7.1040</electronic-resource-num></record></Cite><Cite><Author>Dokken</Author><Year>2008</Year><RecNum>463</RecNum><record><rec-number>463</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">463</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dokken, B. B.</author><author>Saengsirisuwan, V.</author><author>Kim, J. S.</author><author>Teachey, M. K.</author><author>Henriksen, E. J.</author></authors></contributors><auth-address>Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine, Tucson, Arizona 85721-0093, USA.</auth-address><titles><title>Oxidative stress-induced insulin resistance in rat skeletal muscle: role of glycogen synthase kinase-3</title><secondary-title>Am J Physiol Endocrinol Metab</secondary-title><alt-title>American journal of physiology. Endocrinology and metabolism</alt-title></titles><periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></alt-periodical><pages>E615-21</pages><volume>294</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Biological Transport</keyword><keyword>Female</keyword><keyword>Glucose/metabolism</keyword><keyword>Glycogen/biosynthesis</keyword><keyword>Glycogen Synthase/metabolism</keyword><keyword>Glycogen Synthase Kinase 3/antagonists &amp; inhibitors/*physiology</keyword><keyword>Hydrogen Peroxide/pharmacology</keyword><keyword>Insulin/pharmacology</keyword><keyword>*Insulin Resistance</keyword><keyword>Muscle, Skeletal/drug effects/*enzymology</keyword><keyword>Oxidative Stress/*physiology</keyword><keyword>Phosphorylation</keyword><keyword>Rats</keyword><keyword>Rats, Zucker</keyword><keyword>Receptor, Insulin/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0193-1849 (Print)&#xD;0193-1849 (Linking)</isbn><accession-num>18089761</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18089761</url></related-urls></urls><electronic-resource-num>10.1152/ajpendo.00578.2007</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Rudich</Author><Year>1998</Year><RecNum>462</RecNum><DisplayText>[205, 207, 208]</DisplayText><record><rec-number>462</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">462</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rudich, A.</author><author>Tirosh, A.</author><author>Potashnik, R.</author><author>Hemi, R.</author><author>Kanety, H.</author><author>Bashan, N.</author></authors></contributors><auth-address>Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.</auth-address><titles><title>Prolonged oxidative stress impairs insulin-induced GLUT4 translocation in 3T3-L1 adipocytes</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>1562-9</pages><volume>47</volume><number>10</number><keywords><keyword>3T3 Cells</keyword><keyword>Adipocytes/*drug effects/*metabolism/ultrastructure</keyword><keyword>Animals</keyword><keyword>Biological Transport</keyword><keyword>Cell Membrane/metabolism</keyword><keyword>Deoxyglucose/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Glucose Transporter Type 1</keyword><keyword>Glucose Transporter Type 4</keyword><keyword>Hydrogen Peroxide/pharmacology</keyword><keyword>Insulin/*pharmacology</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Mice</keyword><keyword>Microsomes/enzymology</keyword><keyword>Monosaccharide Transport Proteins/*metabolism</keyword><keyword>*Muscle Proteins</keyword><keyword>Osmolar Concentration</keyword><keyword>*Oxidative Stress</keyword><keyword>Phosphatidylinositol 3-Kinases/metabolism</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword></keywords><dates><year>1998</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0012-1797 (Print)&#xD;0012-1797 (Linking)</isbn><accession-num>9753293</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9753293</url></related-urls></urls></record></Cite><Cite><Author>Evans</Author><Year>2005</Year><RecNum>460</RecNum><record><rec-number>460</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">460</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Evans, J. L.</author><author>Maddux, B. A.</author><author>Goldfine, I. D.</author></authors></contributors><auth-address>Medical Research Institute, San Francisco, CA 94107, USA. jevansphd@earthlink.net</auth-address><titles><title>The molecular basis for oxidative stress-induced insulin resistance</title><secondary-title>Antioxid Redox Signal</secondary-title><alt-title>Antioxidants &amp; redox signaling</alt-title></titles><periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></periodical><alt-periodical><full-title>Antioxid Redox Signal</full-title><abbr-1>Antioxidants &amp; redox signaling</abbr-1></alt-periodical><pages>1040-52</pages><volume>7</volume><number>7-8</number><keywords><keyword>Animals</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Oxidation-Reduction</keyword><keyword>*Oxidative Stress</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>1523-0864 (Print)&#xD;1523-0864 (Linking)</isbn><accession-num>15998259</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15998259</url></related-urls></urls><electronic-resource-num>10.1089/ars.2005.7.1040</electronic-resource-num></record></Cite><Cite><Author>Dokken</Author><Year>2008</Year><RecNum>463</RecNum><record><rec-number>463</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">463</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dokken, B. B.</author><author>Saengsirisuwan, V.</author><author>Kim, J. S.</author><author>Teachey, M. K.</author><author>Henriksen, E. J.</author></authors></contributors><auth-address>Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine, Tucson, Arizona 85721-0093, USA.</auth-address><titles><title>Oxidative stress-induced insulin resistance in rat skeletal muscle: role of glycogen synthase kinase-3</title><secondary-title>Am J Physiol Endocrinol Metab</secondary-title><alt-title>American journal of physiology. Endocrinology and metabolism</alt-title></titles><periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></alt-periodical><pages>E615-21</pages><volume>294</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Biological Transport</keyword><keyword>Female</keyword><keyword>Glucose/metabolism</keyword><keyword>Glycogen/biosynthesis</keyword><keyword>Glycogen Synthase/metabolism</keyword><keyword>Glycogen Synthase Kinase 3/antagonists &amp; inhibitors/*physiology</keyword><keyword>Hydrogen Peroxide/pharmacology</keyword><keyword>Insulin/pharmacology</keyword><keyword>*Insulin Resistance</keyword><keyword>Muscle, Skeletal/drug effects/*enzymology</keyword><keyword>Oxidative Stress/*physiology</keyword><keyword>Phosphorylation</keyword><keyword>Rats</keyword><keyword>Rats, Zucker</keyword><keyword>Receptor, Insulin/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0193-1849 (Print)&#xD;0193-1849 (Linking)</isbn><accession-num>18089761</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18089761</url></related-urls></urls><electronic-resource-num>10.1152/ajpendo.00578.2007</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 205, 207, 208. In addition to ROS formation and oxidative stress, alteration in mitochondrial dynamics like increased mitochondrial fission also leads to IR due to decreases activity of IRS-1 and Akt and can be rescued upon inhibition of fission 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 209. Further mitochondrial dysfunction impairs fatty acid oxidation which results in IR via DAG mediated PKC-1 activation in liver 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 210, 211 and ceramides mediated inhibition of Akt in muscle 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 212, 213.1.4.3.e.ER stress:The ER stress or unfolded protein response (UPR) is a primarily adaptive process that ensures proper functioning of ER. However, when UPR fails to restore ER homeostasis, it triggers cell death usually by inducing apoptosis, representing the last choice of multicellular organisms to dispense of dysfunctional cells. Unresolved ER stress and sustained activation of UPR contribute to IR. The link between ER stress and IR is evinced by the similarity in the causative factors such as hyperglycemia, enhanced saturated free fatty acids, and obesity. A large number of in vitro and in vivo studies, as well as investigations in patients with T2D and obesity have confirmed the contribution of ER stress in the development of T2D ADDIN EN.CITE <EndNote><Cite><Author>Schonthal</Author><Year>2012</Year><RecNum>639</RecNum><DisplayText>214</DisplayText><record><rec-number>639</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>639</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Schonthal, A. H.</author></authors></contributors><auth-address>Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR-405, Los Angeles, CA 90033, USA.</auth-address><titles><title>Endoplasmic reticulum stress: its role in disease and novel prospects for therapy</title><secondary-title>Scientifica (Cairo)</secondary-title><alt-title>Scientifica</alt-title></titles><periodical><full-title>Scientifica (Cairo)</full-title><abbr-1>Scientifica</abbr-1></periodical><alt-periodical><full-title>Scientifica (Cairo)</full-title><abbr-1>Scientifica</abbr-1></alt-periodical><pages>857516</pages><volume>2012</volume><dates><year>2012</year></dates><isbn>2090-908X (Print) 2090-908X (Linking)</isbn><accession-num>24278747</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24278747</url></related-urls></urls><custom2>3820435</custom2><electronic-resource-num>10.6064/2012/857516</electronic-resource-num></record></Cite></EndNote>214Activation of the three UPR signalling pathways (PERK, IRE1, and ATF6) is detected in obese patients that act to reduce the burden of unfolded proteins ADDIN EN.CITE <EndNote><Cite><Author>Hotamisligil</Author><Year>2010</Year><RecNum>467</RecNum><DisplayText>215</DisplayText><record><rec-number>467</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>467</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Hotamisligil, G. S.</author></authors></contributors><auth-address>Department of Genetics and Complex Diseases, Broad Institute of Harvard and MIT, Harvard School of Public Health, Boston, MA 02115, USA. [email protected]</auth-address><titles><title>Endoplasmic reticulum stress and the inflammatory basis of metabolic disease</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>900-17</pages><volume>140</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Humans</keyword><keyword>Inflammation/immunology/physiopathology</keyword><keyword>Metabolic Diseases/immunology/*physiopathology</keyword><keyword>Protein Folding</keyword><keyword>Stress, Physiological</keyword><keyword>*Unfolded Protein Response</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar 19</date></pub-dates></dates><isbn>1097-4172 (Electronic) 0092-8674 (Linking)</isbn><accession-num>20303879</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20303879</url></related-urls></urls><custom2>2887297</custom2><electronic-resource-num>10.1016/j.cell.2010.02.034</electronic-resource-num></record></Cite></EndNote>215. ER stress contributes to IR primarily by progressive decline pancreatic ?-cell function and ?-cell mass ADDIN EN.CITE <EndNote><Cite><Author>Fonseca</Author><Year>2011</Year><RecNum>522</RecNum><DisplayText>216</DisplayText><record><rec-number>522</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>522</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Fonseca, S. G.</author><author>Gromada, J.</author><author>Urano, F.</author></authors></contributors><auth-address>Cardiovascular and Metabolism Disease Area, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.</auth-address><titles><title>Endoplasmic reticulum stress and pancreatic beta-cell death</title><secondary-title>Trends Endocrinol Metab</secondary-title><alt-title>Trends in endocrinology and metabolism: TEM</alt-title></titles><periodical><full-title>Trends Endocrinol Metab</full-title><abbr-1>Trends in endocrinology and metabolism: TEM</abbr-1></periodical><alt-periodical><full-title>Trends Endocrinol Metab</full-title><abbr-1>Trends in endocrinology and metabolism: TEM</abbr-1></alt-periodical><pages>266-74</pages><volume>22</volume><number>7</number><keywords><keyword>Animals</keyword><keyword>Cell Death</keyword><keyword>Diabetes Mellitus/drug therapy/metabolism/prevention & control</keyword><keyword>Disease Progression</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin-Secreting Cells/*metabolism</keyword><keyword>Molecular Targeted Therapy</keyword><keyword>Oxidative Stress</keyword><keyword>Protein Biosynthesis</keyword><keyword>*Stress, Physiological</keyword><keyword>Unfolded Protein Response</keyword></keywords><dates><year>2011</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1879-3061 (Electronic) 1043-2760 (Linking)</isbn><accession-num>21458293</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21458293</url></related-urls></urls><custom2>3130122</custom2><electronic-resource-num>10.1016/j.tem.2011.02.008</electronic-resource-num></record></Cite></EndNote>216 as well as induces peripheral IR by phosphorylation of IRS-1 on Ser-307 via activation of JNK and IKK 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 142. Further, compounds like 4-phenyl butyric acid (4-PBA) and taurine-conjugated ursodeoxycholic acid (TUDCA), that are known to alleviate ER stress have shown to restore normal insulin sensitivity in obese animals, consolidating the association of ER stress with IR 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 217, 218. Detailed studies about IR associated ER stress is discussed in the next section. 1.5.Endoplasmic Reticulum Stress and Unfolded Protein response:The ER (endoplasmic reticulum) is an extremely dynamic organelle with complex functionalities which are regulated by multitude parameters of the cell inside as well as in its microenvironment. Such factors include intracellular calcium levels or the redox milieu, certain micro-environmental conditions like availability of oxygen (hypoxia) or glucose (hypoglycemia) and other factors such as high-fat and high-sugar diet, a variety of natural and synthetic compounds (e.g., thapsigargin, tunicamycin, and geldanamycin), and prescription drugs (e.g., bortezomib/Velcade, celecoxib/Celebrex, and nelfinavir/Viracept) can impact protein folding in the lumen of the ER ADDIN EN.CITE <EndNote><Cite><Author>Schroder</Author><Year>2005</Year><RecNum>475</RecNum><DisplayText>219</DisplayText><record><rec-number>475</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>475</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Schroder, M.</author><author>Kaufman, R. J.</author></authors></contributors><auth-address>School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK.</auth-address><titles><title>ER stress and the unfolded protein response</title><secondary-title>Mutat Res</secondary-title><alt-title>Mutation research</alt-title></titles><periodical><full-title>Mutat Res</full-title><abbr-1>Mutation research</abbr-1></periodical><alt-periodical><full-title>Mutat Res</full-title><abbr-1>Mutation research</abbr-1></alt-periodical><pages>29-63</pages><volume>569</volume><number>1-2</number><keywords><keyword>Animals</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Metabolic Diseases/metabolism</keyword><keyword>Molecular Chaperones/metabolism</keyword><keyword>*Oxidative Stress</keyword><keyword>*Protein Folding</keyword><keyword>Signal Transduction/*physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Jan 6</date></pub-dates></dates><isbn>0027-5107 (Print) 0027-5107 (Linking)</isbn><accession-num>15603751</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15603751</url></related-urls></urls><electronic-resource-num>10.1016/j.mrfmmm.2004.06.056</electronic-resource-num></record></Cite></EndNote>219. Accumulation of unfolded or misfolded proteins in the ER activates an evolutionarily conserved defensive process, called the unfolded protein response (UPR), which is comprised of multifaceted cellular mechanisms aimed at adaptation and safeguarding cellular survival initially (Figure 1.5), but can eventually trigger cell death by initiation of apoptosis if ER dysfunction is severe or prolonged to eliminate these faulty cells 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ADDIN EN.CITE.DATA 219, 220. Thus, the sequence of events observed during ER stress can be categorized into three phases of adaptation, alarm, and apoptosis.1.5.1.Adaptation Phase: mechanisms to restore ER homeostasis:1.5.1.a. Recognition of unfolded proteins:BiP/GRP78/Kar2p is an ER resident chaperon of HSP70 class and acts as the stress sensor of ER to recognise unfolded proteins. Under physiological conditions, BiP remains attached to the N-termini of three transmembrane ER proteins and prevent their activation. BiP binds to inositol-requiring enzyme 1? (IRE1?) masking an important oligomerization motif 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ADDIN EN.CITE.DATA 221 and indirectly interferes with oligomerization of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) by inducing steric hindrance or conformational changes in the luminal domain ADDIN EN.CITE <EndNote><Cite><Author>Ma</Author><Year>2002</Year><RecNum>526</RecNum><DisplayText>222</DisplayText><record><rec-number>526</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>526</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ma, K.</author><author>Vattem, K. M.</author><author>Wek, R. C.</author></authors></contributors><auth-address>Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.</auth-address><titles><title>Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>18728-35</pages><volume>277</volume><number>21</number><keywords><keyword>Cell Line</keyword><keyword>Dimerization</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Enzyme Activation</keyword><keyword>Humans</keyword><keyword>Molecular Chaperones/antagonists & inhibitors/*metabolism</keyword><keyword>eIF-2 Kinase/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>May 24</date></pub-dates></dates><isbn>0021-9258 (Print) 0021-9258 (Linking)</isbn><accession-num>11907036</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11907036</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M200903200</electronic-resource-num></record></Cite></EndNote>222. Further, BiP interacts with GLS1 (Golgi localization sequences 1) of Activating transcription factor 6 (ATF6) to inhibit its translocation to Golgi for activation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 223. In addition, ATF6 is retained in the ER by interaction with the lectin calreticulin 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 224. However, upon ER stress, the accumulating misfolded proteins in the ER lumen competitively titrates BiP away from the luminal domains of IRE1 and PERK resulting in the activation of these transmembrane signalling proteins to launch the UPR 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 225, 226. In addition to BiP, IRE-1? ADDIN EN.CITE <EndNote><Cite><Author>Oikawa</Author><Year>2012</Year><RecNum>532</RecNum><DisplayText>227</DisplayText><record><rec-number>532</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>532</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Oikawa, D.</author><author>Kitamura, A.</author><author>Kinjo, M.</author><author>Iwawaki, T.</author></authors></contributors><auth-address>Iwawaki lab, Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi, Gunma, Japan. [email protected]</auth-address><titles><title>Direct association of unfolded proteins with mammalian ER stress sensor, IRE1beta</title><secondary-title>PLoS One</secondary-title><alt-title>PloS one</alt-title></titles><periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></periodical><alt-periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></alt-periodical><pages>e51290</pages><volume>7</volume><number>12</number><keywords><keyword>Endoplasmic Reticulum Stress/*physiology</keyword><keyword>Endoribonucleases/*metabolism</keyword><keyword>HEK293 Cells</keyword><keyword>HeLa Cells</keyword><keyword>Heat-Shock Proteins/*metabolism</keyword><keyword>Humans</keyword><keyword>Membrane Proteins/*metabolism</keyword><keyword>Microscopy, Fluorescence</keyword><keyword>Protein-Serine-Threonine Kinases/*metabolism</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Spectrometry, Fluorescence</keyword><keyword>Unfolded Protein Response/*physiology</keyword></keywords><dates><year>2012</year></dates><isbn>1932-6203 (Electronic) 1932-6203 (Linking)</isbn><accession-num>23236464</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23236464</url></related-urls></urls><custom2>3517461</custom2><electronic-resource-num>10.1371/journal.pone.0051290</electronic-resource-num></record></Cite></EndNote>227 and thioredoxin-interacting protein (TXNIP) 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ADDIN EN.CITE.DATA 228 can also act as a sensor for the recognition of unfolded proteins.1.5.1.b. Transduction of the unfolded protein signal across the ER membrane:Activation of IRE1: The IRE1 pathway is evolutionarily the oldest pathway and is present in all eukaryotes ADDIN EN.CITE <EndNote><Cite><Author>Nikawa</Author><Year>1992</Year><RecNum>533</RecNum><DisplayText>229</DisplayText><record><rec-number>533</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>533</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Nikawa, J.</author><author>Yamashita, S.</author></authors></contributors><auth-address>Department of Biochemistry, Gunma University School of Medicine, Maebashi, Japan.</auth-address><titles><title>IRE1 encodes a putative protein kinase containing a membrane-spanning domain and is required for inositol phototrophy in Saccharomyces cerevisiae</title><secondary-title>Mol Microbiol</secondary-title><alt-title>Molecular microbiology</alt-title></titles><periodical><full-title>Mol Microbiol</full-title><abbr-1>Molecular microbiology</abbr-1></periodical><alt-periodical><full-title>Mol Microbiol</full-title><abbr-1>Molecular microbiology</abbr-1></alt-periodical><pages>1441-6</pages><volume>6</volume><number>11</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Base Sequence</keyword><keyword>Cloning, Molecular</keyword><keyword>Genes, Fungal/*genetics/physiology</keyword><keyword>Inositol/*biosynthesis</keyword><keyword>Molecular Sequence Data</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinases/genetics</keyword><keyword>Saccharomyces cerevisiae/*genetics/metabolism</keyword></keywords><dates><year>1992</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0950-382X (Print) 0950-382X (Linking)</isbn><accession-num>1625574</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/1625574</url></related-urls></urls></record></Cite></EndNote>229 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 230, 231. The IRE1 pathway regulates chaperone induction, ERAD, and expansion of the ER in response to ER stress. IRE1 encodes an atypical type I transmembrane protein kinase endoribonuclease 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ADDIN EN.CITE 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Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwOTItODY3NCAoUHJpbnQpJiN4RDswMDkyLTg2NzQgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjgzNTg3OTQ8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHA6Ly93d3cubmNiaS5ubG0ubmloLmdvdi9wdWJtZWQvODM1ODc5NDwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB= ADDIN EN.CITE.DATA 229, 232, comprising of an ER luminal dimerization domain, and cytosolic kinase and endoribonuclease domains. In mammals IRE1is present in two forms, IRE1? 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 230 and IRE1? 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 231. IRE1? is ubiquitously expressed 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 230, 233, and IRE1?-/- mice are embryonic lethal 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 233, Ire1??/? mice are viable, but are more susceptible to dextran sodium sulphate-induced colitis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 234 as the expression of IRE1? is limited to the gut. After dissociation of BiP from the ER luminal domain, IRE1 oligomerizes or homodimerizes and activates its RNase domain by trans-autophosphorylation at Ser724 ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2014</Year><RecNum>473</RecNum><DisplayText>235</DisplayText><record><rec-number>473</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>473</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lee, J.</author><author>Ozcan, U.</author></authors></contributors><auth-address>From the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.</auth-address><titles><title>Unfolded protein response signaling and metabolic diseases</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>1203-11</pages><volume>289</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism/pathology/therapy</keyword><keyword>Endoplasmic Reticulum/metabolism/pathology</keyword><keyword>*Endoplasmic Reticulum Stress</keyword><keyword>Humans</keyword><keyword>Obesity/*metabolism/pathology/therapy</keyword><keyword>Protein Transport</keyword><keyword>*Signal Transduction</keyword><keyword>*Unfolded Protein Response</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan 17</date></pub-dates></dates><isbn>1083-351X (Electronic) 0021-9258 (Linking)</isbn><accession-num>24324257</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24324257</url></related-urls></urls><custom2>3894306</custom2><electronic-resource-num>10.1074/jbc.R113.534743</electronic-resource-num></record></Cite></EndNote>235, which is responsible for splicing of a diverged group of bZIP transcription factor downstream. The bZIP transcription factor HAC1/XBP1 was the first identified substrate for the yeast Ire1p endoribonuclease <EndNote><Cite><Author>Nojima</Author><Year>1994</Year><RecNum>539</RecNum><DisplayText>[236-238]</DisplayText><record><rec-number>539</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">539</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nojima, H.</author><author>Leem, S. H.</author><author>Araki, H.</author><author>Sakai, A.</author><author>Nakashima, N.</author><author>Kanaoka, Y.</author><author>Ono, Y.</author></authors></contributors><auth-address>Department of Molecular Genetics, Osaka University, Japan.</auth-address><titles><title>Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe</title><secondary-title>Nucleic Acids Res</secondary-title><alt-title>Nucleic acids research</alt-title></titles><periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></periodical><alt-periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></alt-periodical><pages>5279-88</pages><volume>22</volume><number>24</number><keywords><keyword>3&apos;,5&apos;-Cyclic-AMP Phosphodiesterases/antagonists &amp; inhibitors</keyword><keyword>Amino Acid Sequence</keyword><keyword>Base Sequence</keyword><keyword>Basic-Leucine Zipper Transcription Factors</keyword><keyword>Caffeine/pharmacology</keyword><keyword>*Cell Cycle Proteins</keyword><keyword>Cell Division/genetics</keyword><keyword>Cloning, Molecular</keyword><keyword>Cyclic AMP Response Element-Binding Protein/*genetics</keyword><keyword>DNA-Binding Proteins/chemistry/genetics/metabolism</keyword><keyword>Fungal Proteins/chemistry/*genetics/metabolism</keyword><keyword>G-Box Binding Factors</keyword><keyword>GTP Phosphohydrolases</keyword><keyword>Gene Expression Regulation, Fungal/*genetics</keyword><keyword>Genes, Fungal/genetics</keyword><keyword>Genes, Suppressor/*genetics</keyword><keyword>Genetic Complementation Test</keyword><keyword>*Leucine Zippers</keyword><keyword>Membrane Proteins</keyword><keyword>Molecular Sequence Data</keyword><keyword>Polydeoxyribonucleotides/chemical synthesis/metabolism</keyword><keyword>Recombinant Fusion Proteins/biosynthesis</keyword><keyword>Repressor Proteins/chemistry/*genetics/metabolism</keyword><keyword>Restriction Mapping</keyword><keyword>*Saccharomyces cerevisiae Proteins</keyword><keyword>Schizosaccharomyces/*genetics/physiology</keyword><keyword>Schizosaccharomyces pombe Proteins</keyword><keyword>Sequence Alignment</keyword><keyword>Sequence Analysis, DNA</keyword><keyword>Sequence Homology, Amino Acid</keyword><keyword>Transcription Factors/genetics</keyword></keywords><dates><year>1994</year><pub-dates><date>Dec 11</date></pub-dates></dates><isbn>0305-1048 (Print)&#xD;0305-1048 (Linking)</isbn><accession-num>7816617</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/7816617</url></related-urls></urls><custom2>332072</custom2></record></Cite><Cite><Author>Mori</Author><Year>1996</Year><RecNum>540</RecNum><record><rec-number>540</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">540</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mori, K.</author><author>Kawahara, T.</author><author>Yoshida, H.</author><author>Yanagi, H.</author><author>Yura, T.</author></authors></contributors><auth-address>HSP Research Institute, Kyoto Research Park, Shimogyo-ku, Japan.</auth-address><titles><title>Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway</title><secondary-title>Genes Cells</secondary-title><alt-title>Genes to cells : devoted to molecular &amp; cellular mechanisms</alt-title></titles><periodical><full-title>Genes Cells</full-title><abbr-1>Genes to cells : devoted to molecular &amp; cellular mechanisms</abbr-1></periodical><alt-periodical><full-title>Genes Cells</full-title><abbr-1>Genes to cells : devoted to molecular &amp; cellular mechanisms</abbr-1></alt-periodical><pages>803-17</pages><volume>1</volume><number>9</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Base Sequence</keyword><keyword>Basic-Leucine Zipper Transcription Factors</keyword><keyword>Cell Nucleus/*physiology</keyword><keyword>Chromosome Mapping</keyword><keyword>Cloning, Molecular</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Fungal Proteins/*physiology</keyword><keyword>*Leucine Zippers</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutation</keyword><keyword>*Protein Folding</keyword><keyword>Proteins/metabolism</keyword><keyword>Recombinant Fusion Proteins</keyword><keyword>*Regulatory Sequences, Nucleic Acid</keyword><keyword>Repressor Proteins/*physiology</keyword><keyword>*Saccharomyces cerevisiae Proteins</keyword><keyword>Signal Transduction</keyword><keyword>Transcription Factors/*physiology</keyword><keyword>beta-Galactosidase/genetics</keyword></keywords><dates><year>1996</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1356-9597 (Print)&#xD;1356-9597 (Linking)</isbn><accession-num>9077435</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9077435</url></related-urls></urls></record></Cite><Cite><Author>Nikawa</Author><Year>1996</Year><RecNum>541</RecNum><record><rec-number>541</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">541</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nikawa, J.</author><author>Akiyoshi, M.</author><author>Hirata, S.</author><author>Fukuda, T.</author></authors></contributors><auth-address>Department of Biochemical Engineering and Science, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Fukuoka, Japan. nikawa@bse.kyutech.ac.jp</auth-address><titles><title>Saccharomyces cerevisiae IRE2/HAC1 is involved in IRE1-mediated KAR2 expression</title><secondary-title>Nucleic Acids Res</secondary-title><alt-title>Nucleic acids research</alt-title></titles><periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></periodical><alt-periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></alt-periodical><pages>4222-6</pages><volume>24</volume><number>21</number><keywords><keyword>Anti-Bacterial Agents/pharmacology</keyword><keyword>Basic-Leucine Zipper Transcription Factors</keyword><keyword>Dimerization</keyword><keyword>Escherichia coli</keyword><keyword>Fungal Proteins/*genetics/*metabolism</keyword><keyword>Gene Expression Regulation, Fungal</keyword><keyword>HSP70 Heat-Shock Proteins/*genetics</keyword><keyword>Membrane Glycoproteins/*metabolism</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutagenesis</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Repressor Proteins/*metabolism</keyword><keyword>Saccharomyces cerevisiae/drug effects/*genetics</keyword><keyword>*Saccharomyces cerevisiae Proteins</keyword><keyword>*Transcription Factors</keyword><keyword>Tunicamycin/pharmacology</keyword></keywords><dates><year>1996</year><pub-dates><date>Nov 1</date></pub-dates></dates><isbn>0305-1048 (Print)&#xD;0305-1048 (Linking)</isbn><accession-num>8932376</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/8932376</url></related-urls></urls><custom2>146251</custom2></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Nojima</Author><Year>1994</Year><RecNum>539</RecNum><DisplayText>[236-238]</DisplayText><record><rec-number>539</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">539</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nojima, H.</author><author>Leem, S. H.</author><author>Araki, H.</author><author>Sakai, A.</author><author>Nakashima, N.</author><author>Kanaoka, Y.</author><author>Ono, Y.</author></authors></contributors><auth-address>Department of Molecular Genetics, Osaka University, Japan.</auth-address><titles><title>Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe</title><secondary-title>Nucleic Acids Res</secondary-title><alt-title>Nucleic acids research</alt-title></titles><periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></periodical><alt-periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></alt-periodical><pages>5279-88</pages><volume>22</volume><number>24</number><keywords><keyword>3&apos;,5&apos;-Cyclic-AMP Phosphodiesterases/antagonists &amp; inhibitors</keyword><keyword>Amino Acid Sequence</keyword><keyword>Base Sequence</keyword><keyword>Basic-Leucine Zipper Transcription Factors</keyword><keyword>Caffeine/pharmacology</keyword><keyword>*Cell Cycle Proteins</keyword><keyword>Cell Division/genetics</keyword><keyword>Cloning, Molecular</keyword><keyword>Cyclic AMP Response Element-Binding Protein/*genetics</keyword><keyword>DNA-Binding Proteins/chemistry/genetics/metabolism</keyword><keyword>Fungal Proteins/chemistry/*genetics/metabolism</keyword><keyword>G-Box Binding Factors</keyword><keyword>GTP Phosphohydrolases</keyword><keyword>Gene Expression Regulation, Fungal/*genetics</keyword><keyword>Genes, Fungal/genetics</keyword><keyword>Genes, Suppressor/*genetics</keyword><keyword>Genetic Complementation Test</keyword><keyword>*Leucine Zippers</keyword><keyword>Membrane Proteins</keyword><keyword>Molecular Sequence Data</keyword><keyword>Polydeoxyribonucleotides/chemical synthesis/metabolism</keyword><keyword>Recombinant Fusion Proteins/biosynthesis</keyword><keyword>Repressor Proteins/chemistry/*genetics/metabolism</keyword><keyword>Restriction Mapping</keyword><keyword>*Saccharomyces cerevisiae Proteins</keyword><keyword>Schizosaccharomyces/*genetics/physiology</keyword><keyword>Schizosaccharomyces pombe Proteins</keyword><keyword>Sequence Alignment</keyword><keyword>Sequence Analysis, DNA</keyword><keyword>Sequence Homology, Amino Acid</keyword><keyword>Transcription Factors/genetics</keyword></keywords><dates><year>1994</year><pub-dates><date>Dec 11</date></pub-dates></dates><isbn>0305-1048 (Print)&#xD;0305-1048 (Linking)</isbn><accession-num>7816617</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/7816617</url></related-urls></urls><custom2>332072</custom2></record></Cite><Cite><Author>Mori</Author><Year>1996</Year><RecNum>540</RecNum><record><rec-number>540</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">540</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mori, K.</author><author>Kawahara, T.</author><author>Yoshida, H.</author><author>Yanagi, H.</author><author>Yura, T.</author></authors></contributors><auth-address>HSP Research Institute, Kyoto Research Park, Shimogyo-ku, Japan.</auth-address><titles><title>Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway</title><secondary-title>Genes Cells</secondary-title><alt-title>Genes to cells : devoted to molecular &amp; cellular mechanisms</alt-title></titles><periodical><full-title>Genes Cells</full-title><abbr-1>Genes to cells : devoted to molecular &amp; cellular mechanisms</abbr-1></periodical><alt-periodical><full-title>Genes Cells</full-title><abbr-1>Genes to cells : devoted to molecular &amp; cellular mechanisms</abbr-1></alt-periodical><pages>803-17</pages><volume>1</volume><number>9</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Base Sequence</keyword><keyword>Basic-Leucine Zipper Transcription Factors</keyword><keyword>Cell Nucleus/*physiology</keyword><keyword>Chromosome Mapping</keyword><keyword>Cloning, Molecular</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Fungal Proteins/*physiology</keyword><keyword>*Leucine Zippers</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutation</keyword><keyword>*Protein Folding</keyword><keyword>Proteins/metabolism</keyword><keyword>Recombinant Fusion Proteins</keyword><keyword>*Regulatory Sequences, Nucleic Acid</keyword><keyword>Repressor Proteins/*physiology</keyword><keyword>*Saccharomyces cerevisiae Proteins</keyword><keyword>Signal Transduction</keyword><keyword>Transcription Factors/*physiology</keyword><keyword>beta-Galactosidase/genetics</keyword></keywords><dates><year>1996</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1356-9597 (Print)&#xD;1356-9597 (Linking)</isbn><accession-num>9077435</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9077435</url></related-urls></urls></record></Cite><Cite><Author>Nikawa</Author><Year>1996</Year><RecNum>541</RecNum><record><rec-number>541</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">541</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nikawa, J.</author><author>Akiyoshi, M.</author><author>Hirata, S.</author><author>Fukuda, T.</author></authors></contributors><auth-address>Department of Biochemical Engineering and Science, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Fukuoka, Japan. nikawa@bse.kyutech.ac.jp</auth-address><titles><title>Saccharomyces cerevisiae IRE2/HAC1 is involved in IRE1-mediated KAR2 expression</title><secondary-title>Nucleic Acids Res</secondary-title><alt-title>Nucleic acids research</alt-title></titles><periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></periodical><alt-periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></alt-periodical><pages>4222-6</pages><volume>24</volume><number>21</number><keywords><keyword>Anti-Bacterial Agents/pharmacology</keyword><keyword>Basic-Leucine Zipper Transcription Factors</keyword><keyword>Dimerization</keyword><keyword>Escherichia coli</keyword><keyword>Fungal Proteins/*genetics/*metabolism</keyword><keyword>Gene Expression Regulation, Fungal</keyword><keyword>HSP70 Heat-Shock Proteins/*genetics</keyword><keyword>Membrane Glycoproteins/*metabolism</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutagenesis</keyword><keyword>*Protein-Serine-Threonine Kinases</keyword><keyword>Repressor Proteins/*metabolism</keyword><keyword>Saccharomyces cerevisiae/drug effects/*genetics</keyword><keyword>*Saccharomyces cerevisiae Proteins</keyword><keyword>*Transcription Factors</keyword><keyword>Tunicamycin/pharmacology</keyword></keywords><dates><year>1996</year><pub-dates><date>Nov 1</date></pub-dates></dates><isbn>0305-1048 (Print)&#xD;0305-1048 (Linking)</isbn><accession-num>8932376</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/8932376</url></related-urls></urls><custom2>146251</custom2></record></Cite></EndNote> ADDIN EN.CITE.DATA 236-238. Activated Ire1p cleaves both 5′ and 3′ exon-intron junctions in mRNA and introduces a frame-shift and an alternative C-terminus with increased transcriptional activation potential. IRE1 pathway coordinates multiple functions like chaperone induction, upregulation of ERAD genes, membrane biogenesis, retrograde transport of misfolded protein from ER to the cytosol and ER quality-control ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2014</Year><RecNum>473</RecNum><DisplayText>235</DisplayText><record><rec-number>473</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>473</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lee, J.</author><author>Ozcan, U.</author></authors></contributors><auth-address>From the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.</auth-address><titles><title>Unfolded protein response signaling and metabolic diseases</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>1203-11</pages><volume>289</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism/pathology/therapy</keyword><keyword>Endoplasmic Reticulum/metabolism/pathology</keyword><keyword>*Endoplasmic Reticulum Stress</keyword><keyword>Humans</keyword><keyword>Obesity/*metabolism/pathology/therapy</keyword><keyword>Protein Transport</keyword><keyword>*Signal Transduction</keyword><keyword>*Unfolded Protein Response</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan 17</date></pub-dates></dates><isbn>1083-351X (Electronic) 0021-9258 (Linking)</isbn><accession-num>24324257</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24324257</url></related-urls></urls><custom2>3894306</custom2><electronic-resource-num>10.1074/jbc.R113.534743</electronic-resource-num></record></Cite></EndNote>235. Apart from regulating ER-resident molecular chaperones, XBP-1 is also involved in adipogenesis, lipid metabolism and inflammation ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2014</Year><RecNum>473</RecNum><DisplayText>235</DisplayText><record><rec-number>473</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>473</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lee, J.</author><author>Ozcan, U.</author></authors></contributors><auth-address>From the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.</auth-address><titles><title>Unfolded protein response signaling and metabolic diseases</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>1203-11</pages><volume>289</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism/pathology/therapy</keyword><keyword>Endoplasmic Reticulum/metabolism/pathology</keyword><keyword>*Endoplasmic Reticulum Stress</keyword><keyword>Humans</keyword><keyword>Obesity/*metabolism/pathology/therapy</keyword><keyword>Protein Transport</keyword><keyword>*Signal Transduction</keyword><keyword>*Unfolded Protein Response</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan 17</date></pub-dates></dates><isbn>1083-351X (Electronic) 0021-9258 (Linking)</isbn><accession-num>24324257</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24324257</url></related-urls></urls><custom2>3894306</custom2><electronic-resource-num>10.1074/jbc.R113.534743</electronic-resource-num></record></Cite></EndNote>235.Activation of PERK:Upon removal of BiP, PERK oligomerizes in ER membranes, inducing its autophosphorylation and activating the kinase domain. PERK phosphorylates its substrate proteins, eIF2? ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2014</Year><RecNum>473</RecNum><DisplayText>235</DisplayText><record><rec-number>473</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>473</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lee, J.</author><author>Ozcan, U.</author></authors></contributors><auth-address>From the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.</auth-address><titles><title>Unfolded protein response signaling and metabolic diseases</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>1203-11</pages><volume>289</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism/pathology/therapy</keyword><keyword>Endoplasmic Reticulum/metabolism/pathology</keyword><keyword>*Endoplasmic Reticulum Stress</keyword><keyword>Humans</keyword><keyword>Obesity/*metabolism/pathology/therapy</keyword><keyword>Protein Transport</keyword><keyword>*Signal Transduction</keyword><keyword>*Unfolded Protein Response</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan 17</date></pub-dates></dates><isbn>1083-351X (Electronic) 0021-9258 (Linking)</isbn><accession-num>24324257</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24324257</url></related-urls></urls><custom2>3894306</custom2><electronic-resource-num>10.1074/jbc.R113.534743</electronic-resource-num></record></Cite></EndNote>235 and the bZIP Cap’n’Collar transcription factor Nrf2 (nuclear factor erythroid 2–related factor 2) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 239. Phosphorylation of eIF2? by PERK shuts-off cap-dependent translation and activates IRES-mediated translation for genes like ATF4 which controls the expression of genes regulating the amino acid import, glutathione biosynthesis, and resistance to oxidative stress 38. Perk?/? cells are sensitive to ER stress, which is rescued by inhibition of translation by cycloheximide 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 240. The importance of PERK mediated signalling in protection against ER stress is demonstrated by perk–/– cells and knock-in cells expressing non-phosphorylable eIF2?(S51A) that display hypersensitivity to ER stress 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 240, 241.Besides eIF2?, PERK also phosphorylates the antioxidant transcription factor Nrf2. Upon activation, PERK phosphorylates Nrf2 that promotes its transcription activation through the antioxidant response element (ARE) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 242, 243. Genes regulated by the ARE include the A1 and A2 subunits of glutathione S-transferase, NAD(P)H: quinone oxidoreductase, ?-glutamylcysteine synthetase, and UDP-glucuronosyl transferase. ARE also controls expressions of genes involved in the phase II metabolism of xenobiotics, e.g. electrophilic thiol-reactive substances that mimic an oxidative insult. Perk?/? cells accumulate reactive oxygen species when exposed to ER stress 38 which suggests that the sensitivity of Nrf2?/? cells to ER stress 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 239 results from their impaired ability to respond to an oxidative insult.However, if ER homeostasis is achieved, translation is resumed by a negative feedback mechanism that inactive PERK by activation of P58IPK and GADD34 late in ER stress. P58IPK, activated by ATF6, inhibits PERK by binding to its kinase domain 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 244, 245, while, GADD34, expressed upon activation of ATF4 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 246, 247, targets PP1 to the ER 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 248 that can dephosphorylate PERK induced eIF2? phosphorylation.Activation of ATF6:Two homologous proteins of ATF6 exist in mammals, ATF6? and ATF6? /CREB-RP 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ADDIN EN.CITE.DATA 249. Upon dissociation of BiP, ATF6 translocates to the Golgi complex ADDIN EN.CITE <EndNote><Cite><Author>Chen</Author><Year>2002</Year><RecNum>553</RecNum><DisplayText>250</DisplayText><record><rec-number>553</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>553</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Chen, X.</author><author>Shen, J.</author><author>Prywes, R.</author></authors></contributors><auth-address>Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, NY 10027, USA.</auth-address><titles><title>The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the ER to the Golgi</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>13045-52</pages><volume>277</volume><number>15</number><keywords><keyword>3T3 Cells</keyword><keyword>Activating Transcription Factor 6</keyword><keyword>Animals</keyword><keyword>DNA-Binding Proteins/*metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Gene Expression Regulation</keyword><keyword>Golgi Apparatus/*metabolism</keyword><keyword>HeLa Cells</keyword><keyword>Humans</keyword><keyword>Hydrolysis</keyword><keyword>Mice</keyword><keyword>Protein Transport</keyword><keyword>Transcription Factors/*metabolism</keyword></keywords><dates><year>2002</year><pub-dates><date>Apr 12</date></pub-dates></dates><isbn>0021-9258 (Print) 0021-9258 (Linking)</isbn><accession-num>11821395</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11821395</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M110636200</electronic-resource-num></record></Cite></EndNote>250, where site-1 protease (S1P) cleaves ATF6 in the luminal domain and then S2P cleaves the N-terminal, membrane-anchored half ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2014</Year><RecNum>473</RecNum><DisplayText>235</DisplayText><record><rec-number>473</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>473</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lee, J.</author><author>Ozcan, U.</author></authors></contributors><auth-address>From the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.</auth-address><titles><title>Unfolded protein response signaling and metabolic diseases</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>1203-11</pages><volume>289</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism/pathology/therapy</keyword><keyword>Endoplasmic Reticulum/metabolism/pathology</keyword><keyword>*Endoplasmic Reticulum Stress</keyword><keyword>Humans</keyword><keyword>Obesity/*metabolism/pathology/therapy</keyword><keyword>Protein Transport</keyword><keyword>*Signal Transduction</keyword><keyword>*Unfolded Protein Response</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan 17</date></pub-dates></dates><isbn>1083-351X (Electronic) 0021-9258 (Linking)</isbn><accession-num>24324257</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24324257</url></related-urls></urls><custom2>3894306</custom2><electronic-resource-num>10.1074/jbc.R113.534743</electronic-resource-num></record></Cite></EndNote>235, releasing the cytosolic N-terminal portion of ATF6 encoding a basic leucine zipper (bZIP) transcription factor. ATF6 binds to the ATF/CRE element 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ADDIN EN.CITE.DATA 253. ATF6 regulates transcription of several UPR elements like BiP, XBP-1, CHOP, P58IPK, the membrane protein Herp <EndNote><Cite><Author>Kokame</Author><Year>2001</Year><RecNum>557</RecNum><DisplayText>[244, 253, 254]</DisplayText><record><rec-number>557</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">557</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kokame, K.</author><author>Kato, H.</author><author>Miyata, T.</author></authors></contributors><auth-address>National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. kame@ri.ncvc.go.jp</auth-address><titles><title>Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>9199-205</pages><volume>276</volume><number>12</number><keywords><keyword>Activating Transcription Factor 6</keyword><keyword>Base Sequence</keyword><keyword>Cloning, Molecular</keyword><keyword>Dna</keyword><keyword>DNA-Binding Proteins/chemistry/*metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Humans</keyword><keyword>Membrane Proteins/chemistry/genetics/*metabolism</keyword><keyword>Molecular Sequence Data</keyword><keyword>Plasmids</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>Protein Denaturation</keyword><keyword>Transcription Factors/chemistry/*metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Mar 23</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>11112790</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11112790</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M010486200</electronic-resource-num></record></Cite><Cite><Author>Yoshida</Author><Year>2000</Year><RecNum>558</RecNum><record><rec-number>558</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">558</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yoshida, H.</author><author>Okada, T.</author><author>Haze, K.</author><author>Yanagi, H.</author><author>Yura, T.</author><author>Negishi, M.</author><author>Mori, K.</author></authors></contributors><auth-address>HSP Research Institute, Kyoto Research Park, Shimogyo-ku, Japan.</auth-address><titles><title>ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>6755-67</pages><volume>20</volume><number>18</number><keywords><keyword>Activating Transcription Factor 6</keyword><keyword>Animals</keyword><keyword>CCAAT-Enhancer-Binding Proteins</keyword><keyword>Carrier Proteins/genetics</keyword><keyword>Cell Extracts</keyword><keyword>Cell Nucleus/metabolism</keyword><keyword>DNA-Binding Proteins/*genetics/*metabolism</keyword><keyword>Endoplasmic Reticulum</keyword><keyword>Gene Expression</keyword><keyword>HeLa Cells</keyword><keyword>*Heat-Shock Proteins</keyword><keyword>Humans</keyword><keyword>Mammals</keyword><keyword>Molecular Chaperones/genetics</keyword><keyword>Mutagenesis</keyword><keyword>Nuclear Proteins/*genetics</keyword><keyword>*Protein Folding</keyword><keyword>Regulatory Factor X Transcription Factors</keyword><keyword>Regulatory Sequences, Nucleic Acid</keyword><keyword>Transcription Factor CHOP</keyword><keyword>Transcription Factors/*genetics/*metabolism</keyword><keyword>Transcription, Genetic</keyword><keyword>X-Box Binding Protein 1</keyword></keywords><dates><year>2000</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>10958673</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10958673</url></related-urls></urls><custom2>86199</custom2></record></Cite><Cite><Author>van Huizen</Author><Year>2003</Year><RecNum>548</RecNum><record><rec-number>548</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">548</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>van Huizen, R.</author><author>Martindale, J. L.</author><author>Gorospe, M.</author><author>Holbrook, N. J.</author></authors></contributors><auth-address>Laboratory of Cellular and Molecular Biology, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. HuizenRi@grc.nia.nih.gov</auth-address><titles><title>P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>15558-64</pages><volume>278</volume><number>18</number><keywords><keyword>Activating Transcription Factor 6</keyword><keyword>Apoptosis</keyword><keyword>CCAAT-Enhancer-Binding Proteins/biosynthesis</keyword><keyword>DNA-Binding Proteins/physiology</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>Eukaryotic Initiation Factor-2/*physiology</keyword><keyword>Gene Silencing</keyword><keyword>HSP40 Heat-Shock Proteins</keyword><keyword>Humans</keyword><keyword>Oligonucleotide Array Sequence Analysis</keyword><keyword>Phosphorylation</keyword><keyword>Protein Folding</keyword><keyword>RNA, Small Interfering</keyword><keyword>Repressor Proteins/genetics/*physiology</keyword><keyword>Transcription Factor CHOP</keyword><keyword>Transcription Factors/biosynthesis/physiology</keyword><keyword>eIF-2 Kinase/metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>May 2</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>12601012</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12601012</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M212074200</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Kokame</Author><Year>2001</Year><RecNum>557</RecNum><DisplayText>[244, 253, 254]</DisplayText><record><rec-number>557</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">557</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kokame, K.</author><author>Kato, H.</author><author>Miyata, T.</author></authors></contributors><auth-address>National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. kame@ri.ncvc.go.jp</auth-address><titles><title>Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>9199-205</pages><volume>276</volume><number>12</number><keywords><keyword>Activating Transcription Factor 6</keyword><keyword>Base Sequence</keyword><keyword>Cloning, Molecular</keyword><keyword>Dna</keyword><keyword>DNA-Binding Proteins/chemistry/*metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Humans</keyword><keyword>Membrane Proteins/chemistry/genetics/*metabolism</keyword><keyword>Molecular Sequence Data</keyword><keyword>Plasmids</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>Protein Denaturation</keyword><keyword>Transcription Factors/chemistry/*metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Mar 23</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>11112790</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11112790</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M010486200</electronic-resource-num></record></Cite><Cite><Author>Yoshida</Author><Year>2000</Year><RecNum>558</RecNum><record><rec-number>558</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">558</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yoshida, H.</author><author>Okada, T.</author><author>Haze, K.</author><author>Yanagi, H.</author><author>Yura, T.</author><author>Negishi, M.</author><author>Mori, K.</author></authors></contributors><auth-address>HSP Research Institute, Kyoto Research Park, Shimogyo-ku, Japan.</auth-address><titles><title>ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>6755-67</pages><volume>20</volume><number>18</number><keywords><keyword>Activating Transcription Factor 6</keyword><keyword>Animals</keyword><keyword>CCAAT-Enhancer-Binding Proteins</keyword><keyword>Carrier Proteins/genetics</keyword><keyword>Cell Extracts</keyword><keyword>Cell Nucleus/metabolism</keyword><keyword>DNA-Binding Proteins/*genetics/*metabolism</keyword><keyword>Endoplasmic Reticulum</keyword><keyword>Gene Expression</keyword><keyword>HeLa Cells</keyword><keyword>*Heat-Shock Proteins</keyword><keyword>Humans</keyword><keyword>Mammals</keyword><keyword>Molecular Chaperones/genetics</keyword><keyword>Mutagenesis</keyword><keyword>Nuclear Proteins/*genetics</keyword><keyword>*Protein Folding</keyword><keyword>Regulatory Factor X Transcription Factors</keyword><keyword>Regulatory Sequences, Nucleic Acid</keyword><keyword>Transcription Factor CHOP</keyword><keyword>Transcription Factors/*genetics/*metabolism</keyword><keyword>Transcription, Genetic</keyword><keyword>X-Box Binding Protein 1</keyword></keywords><dates><year>2000</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>10958673</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10958673</url></related-urls></urls><custom2>86199</custom2></record></Cite><Cite><Author>van Huizen</Author><Year>2003</Year><RecNum>548</RecNum><record><rec-number>548</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">548</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>van Huizen, R.</author><author>Martindale, J. L.</author><author>Gorospe, M.</author><author>Holbrook, N. J.</author></authors></contributors><auth-address>Laboratory of Cellular and Molecular Biology, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. HuizenRi@grc.nia.nih.gov</auth-address><titles><title>P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>15558-64</pages><volume>278</volume><number>18</number><keywords><keyword>Activating Transcription Factor 6</keyword><keyword>Apoptosis</keyword><keyword>CCAAT-Enhancer-Binding Proteins/biosynthesis</keyword><keyword>DNA-Binding Proteins/physiology</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>Eukaryotic Initiation Factor-2/*physiology</keyword><keyword>Gene Silencing</keyword><keyword>HSP40 Heat-Shock Proteins</keyword><keyword>Humans</keyword><keyword>Oligonucleotide Array Sequence Analysis</keyword><keyword>Phosphorylation</keyword><keyword>Protein Folding</keyword><keyword>RNA, Small Interfering</keyword><keyword>Repressor Proteins/genetics/*physiology</keyword><keyword>Transcription Factor CHOP</keyword><keyword>Transcription Factors/biosynthesis/physiology</keyword><keyword>eIF-2 Kinase/metabolism</keyword></keywords><dates><year>2003</year><pub-dates><date>May 2</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>12601012</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12601012</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M212074200</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 244, 253, 254 and other genes involved in ERAD processes and protein folding, maturation and secretion ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2014</Year><RecNum>473</RecNum><DisplayText>235</DisplayText><record><rec-number>473</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>473</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lee, J.</author><author>Ozcan, U.</author></authors></contributors><auth-address>From the Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.</auth-address><titles><title>Unfolded protein response signaling and metabolic diseases</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>1203-11</pages><volume>289</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism/pathology/therapy</keyword><keyword>Endoplasmic Reticulum/metabolism/pathology</keyword><keyword>*Endoplasmic Reticulum Stress</keyword><keyword>Humans</keyword><keyword>Obesity/*metabolism/pathology/therapy</keyword><keyword>Protein Transport</keyword><keyword>*Signal Transduction</keyword><keyword>*Unfolded Protein Response</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan 17</date></pub-dates></dates><isbn>1083-351X (Electronic) 0021-9258 (Linking)</isbn><accession-num>24324257</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24324257</url></related-urls></urls><custom2>3894306</custom2><electronic-resource-num>10.1074/jbc.R113.534743</electronic-resource-num></record></Cite></EndNote>235. Gene profiling analysis using overexpression system revealed homodimer of ATF6 ?(1-373) 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ADDIN EN.CITE.DATA 255 and ATF6? (1-392) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 249 to positively regulate transcription of ER-resident molecular chaperones and foldases, whereas, heterodimeric complexes act as a repressor of the BiP promoter 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 256.1.5.2. Alarm Phase:Activation of inflammatory pathways aggravates the UPR and sounds the alarm for the onset of the unresolved ER stress responses. During the adaptive phase, activation of PERK–eIF2? pathway shuts down the protein translation, which results in a reduction of the IkB?/NF-kB ratio as IkB? compared to NF-kB has shorter half-life leading to nuclear translocation of NF-kB and consequent increase in the expression of pro-inflammatory genes ADDIN EN.CITE <EndNote><Cite><Author>Hotamisligil</Author><Year>2010</Year><RecNum>467</RecNum><DisplayText>215</DisplayText><record><rec-number>467</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>467</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Hotamisligil, G. S.</author></authors></contributors><auth-address>Department of Genetics and Complex Diseases, Broad Institute of Harvard and MIT, Harvard School of Public Health, Boston, MA 02115, USA. [email protected]</auth-address><titles><title>Endoplasmic reticulum stress and the inflammatory basis of metabolic disease</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>900-17</pages><volume>140</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Humans</keyword><keyword>Inflammation/immunology/physiopathology</keyword><keyword>Metabolic Diseases/immunology/*physiopathology</keyword><keyword>Protein Folding</keyword><keyword>Stress, Physiological</keyword><keyword>*Unfolded Protein Response</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar 19</date></pub-dates></dates><isbn>1097-4172 (Electronic) 0092-8674 (Linking)</isbn><accession-num>20303879</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20303879</url></related-urls></urls><custom2>2887297</custom2><electronic-resource-num>10.1016/j.cell.2010.02.034</electronic-resource-num></record></Cite></EndNote>215. Besides this, activated IRE-1? recruits TNF-?-receptor-associated factor 2 (TRAF2) and this complex activates protein?kinases?implicated?in?immunity?and?inflammation,?including JNK and IKK? resulting in activation of AP-1 and NF-kB. Further, XBP1s can also directly increase the transcription of pro-inflammatory cytokines, which can themselves, activate ER stress and maintain the inflammatory state. In addition, both IRE-1? and PERK through ATF5 activates the TXNIP–NLRP3 pathway, resulting in an inflammatory process 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 257, 258. TXNIP induces inflammation through the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin-domain containing 3 (NLRP3) inflammasome activation and inflammatory cytokine production 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ADDIN EN.CITE.DATA 257. Finally, the ATF6 also promotes inflammation via activation of NF-kB, however, the underlying mechanisms are still not known ADDIN EN.CITE <EndNote><Cite><Author>Hotamisligil</Author><Year>2010</Year><RecNum>467</RecNum><DisplayText>215</DisplayText><record><rec-number>467</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>467</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Hotamisligil, G. S.</author></authors></contributors><auth-address>Department of Genetics and Complex Diseases, Broad Institute of Harvard and MIT, Harvard School of Public Health, Boston, MA 02115, USA. [email protected]</auth-address><titles><title>Endoplasmic reticulum stress and the inflammatory basis of metabolic disease</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>900-17</pages><volume>140</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Humans</keyword><keyword>Inflammation/immunology/physiopathology</keyword><keyword>Metabolic Diseases/immunology/*physiopathology</keyword><keyword>Protein Folding</keyword><keyword>Stress, Physiological</keyword><keyword>*Unfolded Protein Response</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar 19</date></pub-dates></dates><isbn>1097-4172 (Electronic) 0092-8674 (Linking)</isbn><accession-num>20303879</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20303879</url></related-urls></urls><custom2>2887297</custom2><electronic-resource-num>10.1016/j.cell.2010.02.034</electronic-resource-num></record></Cite></EndNote>215.1.5.3.Apoptotic Phase:Apoptosis in response to ER stress is a metazoan-specific cellular response. When?protein?misfolding?is?persistent?or?excessive,?ER?stress?triggers?cell?death,?typically?via apoptosis through several?mechanisms,?including direct?activation?of?proteases,?kinases, transcription?factors,?and?Bcl-2–family?proteins?and?their?modulators ADDIN EN.CITE <EndNote><Cite><Author>Xu</Author><Year>2005</Year><RecNum>524</RecNum><DisplayText>220</DisplayText><record><rec-number>524</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>524</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Xu, C.</author><author>Bailly-Maitre, B.</author><author>Reed, J. C.</author></authors></contributors><auth-address>The Burnham Institute for Medical Research, La Jolla, California 92037, USA.</auth-address><titles><title>Endoplasmic reticulum stress: cell life and death decisions</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>2656-64</pages><volume>115</volume><number>10</number><keywords><keyword>Animals</keyword><keyword>Cell Death/drug effects</keyword><keyword>Diabetes Mellitus/drug therapy/*metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Humans</keyword><keyword>Hypoxia/drug therapy/*metabolism</keyword><keyword>Myocardial Reperfusion Injury/drug therapy/*metabolism</keyword><keyword>Neurodegenerative Diseases/drug therapy/*metabolism</keyword><keyword>*Signal Transduction/drug effects</keyword><keyword>Stress, Physiological/metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0021-9738 (Print) 0021-9738 (Linking)</isbn><accession-num>16200199</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16200199</url></related-urls></urls><custom2>1236697</custom2><electronic-resource-num>10.1172/JCI26373</electronic-resource-num></record></Cite></EndNote>220. The topological of ER lumen is comparable to the extracellular space; hence, ER stress is capable of activating both intrinsic and extrinsic apoptotic pathways. The intrinsic pathway is activated in response to intracellular insults, like DNA damage, while the extrinsic pathway responds to extracellular stimuli triggered by self-association of cell surface receptors and recruitment of caspases.1.5.3.a.Intrinsic pathways:Bcl-2/Bax–family?proteins?are?integrated?into?ER?membranes, play an important role in maintaining ER calcium homeostasis and?control?cell?death?induced?by?ER?stress?agents, like tunicamycin, brefeldin?A, thapsigargin,?and oxidants. Upon ER stress Bak and Bax undergo conformational changes and/or oligomerization on ER membrane 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ADDIN EN.CITE.DATA 259, resulting in the release of Ca2+ from the ER lumen. Increase in the Ca2+ levels activates calpain, a?family?of?Ca2+- dependent?cysteine?proteases in the cytosol, which converts ER-localized procaspase-12 to caspase-12 ADDIN EN.CITE <EndNote><Cite><Author>Orrenius</Author><Year>2003</Year><RecNum>565</RecNum><DisplayText>260</DisplayText><record><rec-number>565</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>565</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Orrenius, S.</author><author>Zhivotovsky, B.</author><author>Nicotera, P.</author></authors></contributors><auth-address>Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden. [email protected]</auth-address><titles><title>Regulation of cell death: the calcium-apoptosis link</title><secondary-title>Nat Rev Mol Cell Biol</secondary-title><alt-title>Nature reviews. Molecular cell biology</alt-title></titles><periodical><full-title>Nat Rev Mol Cell Biol</full-title><abbr-1>Nature reviews. Molecular cell biology</abbr-1></periodical><alt-periodical><full-title>Nat Rev Mol Cell Biol</full-title><abbr-1>Nature reviews. Molecular cell biology</abbr-1></alt-periodical><pages>552-65</pages><volume>4</volume><number>7</number><keywords><keyword>Animals</keyword><keyword>*Apoptosis</keyword><keyword>Calcium/*physiology</keyword><keyword>*Calcium Signaling</keyword><keyword>Enzyme Activation</keyword><keyword>Homeostasis</keyword><keyword>Humans</keyword><keyword>Mitochondria/*physiology</keyword><keyword>Necrosis</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2003</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1471-0072 (Print) 1471-0072 (Linking)</isbn><accession-num>12838338</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12838338</url></related-urls></urls><electronic-resource-num>10.1038/nrm1150</electronic-resource-num></record></Cite></EndNote>260. Proteolytic? processing?of?caspase-12 is also detected upon association of caspase-12 with?activated Ire1?in rodents. Activated caspase-12 is then believed to initiate a caspase cascade through cleavage of procaspase-9 and -3 by caspase-9 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 261, 262, independent of Apaf-1 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 262 and mitochondrial cytochrome c release to induce apoptosis. Knockdown of?caspase-12?genes in mice showed partial?resistance?to cell death induced by ER?stress pharmacologically by tunicamycin and thapsigargin. However,?caspase-12 is?absent?in most?human and knockdown?of the?closest?paralogs?of?rodent?caspase-12 in human caspase-4, partially?reduces?cell death induced by? thapsigargin in?human?neuroblastoma?cells, while, in?HeLa?cells?had?little?effect?on?ER-mediated apoptosis,?implying tissue-specificity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 263.Further, excessive release of Ca2+ upon ER stress can also subsequently initiate apoptosis by inducing depolarization of the inner mitochondrial membrane due to the rapid uptake of leaking Ca2+ 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 264, which is blocked by forced expression of Bcl-XL and viral mitochondrial inhibitor of apoptosis (vMIA) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 265. In addition, a tyrosine kinase c-Abl also induces apoptosis upon ER stress. Fibroblasts ablated with c-Abl show resistance?to?cell?death?induced by?Ca2+?ionophores,?brefeldin?A,?and?tunicamycin ADDIN EN.CITE <EndNote><Cite><Author>Ito</Author><Year>2001</Year><RecNum>571</RecNum><DisplayText>266</DisplayText><record><rec-number>571</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>571</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ito, Y.</author><author>Pandey, P.</author><author>Mishra, N.</author><author>Kumar, S.</author><author>Narula, N.</author><author>Kharbanda, S.</author><author>Saxena, S.</author><author>Kufe, D.</author></authors></contributors><auth-address>Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.</auth-address><titles><title>Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>6233-42</pages><volume>21</volume><number>18</number><keywords><keyword>Animals</keyword><keyword>Apoptosis/*physiology</keyword><keyword>Biological Transport/physiology</keyword><keyword>Cell Line</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>Mice</keyword><keyword>Mitochondria/physiology</keyword><keyword>Protein-Tyrosine Kinases/physiology</keyword><keyword>Proto-Oncogene Proteins c-abl/*physiology</keyword><keyword>Rats</keyword><keyword>Signal Transduction/physiology</keyword><keyword>Stress, Mechanical</keyword></keywords><dates><year>2001</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0270-7306 (Print) 0270-7306 (Linking)</isbn><accession-num>11509666</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11509666</url></related-urls></urls><custom2>87342</custom2></record></Cite></EndNote>266. CHOP: ER stress-inducible transcription factors like C/EBP homologous protein (CHOP)/ growth arrest- and DNA damage-inducible gene 153 (GADD153),? is one of the major inducers of apoptosis. The gene expression of CHOP is controlled by ATF4,?ATF6, ATF2?and?XBP-1 ADDIN EN.CITE <EndNote><Cite><Author>Oyadomari</Author><Year>2004</Year><RecNum>572</RecNum><DisplayText>267</DisplayText><record><rec-number>572</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>572</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Oyadomari, S.</author><author>Mori, M.</author></authors></contributors><auth-address>Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan. [email protected]</auth-address><titles><title>Roles of CHOP/GADD153 in endoplasmic reticulum stress</title><secondary-title>Cell Death Differ</secondary-title><alt-title>Cell death and differentiation</alt-title></titles><periodical><full-title>Cell Death Differ</full-title><abbr-1>Cell death and differentiation</abbr-1></periodical><alt-periodical><full-title>Cell Death Differ</full-title><abbr-1>Cell death and differentiation</abbr-1></alt-periodical><pages>381-9</pages><volume>11</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Apoptosis/physiology</keyword><keyword>CCAAT-Enhancer-Binding Proteins/chemistry/*metabolism</keyword><keyword>Cell Differentiation/physiology</keyword><keyword>Cell Division/physiology</keyword><keyword>Disease/etiology</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Stress, Physiological/*metabolism</keyword><keyword>Transcription Factor CHOP</keyword><keyword>Transcription Factors/chemistry/*metabolism</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1350-9047 (Print) 1350-9047 (Linking)</isbn><accession-num>14685163</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14685163</url></related-urls></urls><electronic-resource-num>10.1038/sj.cdd.4401373</electronic-resource-num></record></Cite></EndNote>267. Both PERK and IRE-1 pathway are essential for expression and activation of CHOP. ?Ablation of perk, atf4 and?eIF2?(S51A) expression in cells failed to induce chop expression during ER stress, while, Ire1/ TRAF2/Ask1?pathway brings about p38-mediated phosphorylation of CHOP on?Ser78?&?Ser81?that?increases?its?transcriptional and?apoptotic?activity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 268. The apoptotic effects of CHOP are mostly mediated by suppression of Bcl-2 expression 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 269, 270 but?may?also?have?non-transcriptional actions still?which are poorly?defined? ADDIN EN.CITE <EndNote><Cite><Author>Oyadomari</Author><Year>2004</Year><RecNum>572</RecNum><DisplayText>267</DisplayText><record><rec-number>572</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>572</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Oyadomari, S.</author><author>Mori, M.</author></authors></contributors><auth-address>Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan. [email protected]</auth-address><titles><title>Roles of CHOP/GADD153 in endoplasmic reticulum stress</title><secondary-title>Cell Death Differ</secondary-title><alt-title>Cell death and differentiation</alt-title></titles><periodical><full-title>Cell Death Differ</full-title><abbr-1>Cell death and differentiation</abbr-1></periodical><alt-periodical><full-title>Cell Death Differ</full-title><abbr-1>Cell death and differentiation</abbr-1></alt-periodical><pages>381-9</pages><volume>11</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Apoptosis/physiology</keyword><keyword>CCAAT-Enhancer-Binding Proteins/chemistry/*metabolism</keyword><keyword>Cell Differentiation/physiology</keyword><keyword>Cell Division/physiology</keyword><keyword>Disease/etiology</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Stress, Physiological/*metabolism</keyword><keyword>Transcription Factor CHOP</keyword><keyword>Transcription Factors/chemistry/*metabolism</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1350-9047 (Print) 1350-9047 (Linking)</isbn><accession-num>14685163</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14685163</url></related-urls></urls><electronic-resource-num>10.1038/sj.cdd.4401373</electronic-resource-num></record></Cite></EndNote>267. However, CHOP?is?not?essential?for?cell?death?induced?by?ER?stress,?as the perk–/–?and?eIF2? (S51A) knock-in?cells?are?hypersensitive?to?ER stress-induced?apoptosis?but fail?to?induce?chop?gene?expression?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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 241, 271.1.5.3.b.Extrinsic pathways:The?kinase?Ask1 has been implicated in the induction of extrinsic apoptotic signalling by?cell surface receptors like TNF-family?receptors 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 ADDIN EN.CITE 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ADDIN EN.CITE.DATA 272. During?ER?stress,?Ask1?is activated by binding to oligomerized?Ire1complexes?containing?TRAF2, leading to?activation?of p38 and JNK that induces cell death. Hence, ask1–/–?neurons?failed to induce ER?stress-mediated JNK?activation?and?cell?death?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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 273.?However,?downstream?death?effectors?of?Ask1?are?not?clear. It is assumed that Ask1?leads?to?activation of JNK, which via phosphorylation?activates?proapoptotic Bim proteins?<EndNote><Cite><Author>Lei</Author><Year>2003</Year><RecNum>579</RecNum><DisplayText>[274-276]</DisplayText><record><rec-number>579</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">579</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lei, K.</author><author>Davis, R. J.</author></authors></contributors><auth-address>Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.</auth-address><titles><title>JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>2432-7</pages><volume>100</volume><number>5</number><keywords><keyword>*Adaptor Proteins, Signal Transducing</keyword><keyword>*Apoptosis</keyword><keyword>Apoptosis Regulatory Proteins</keyword><keyword>Bcl-2-Like Protein 11</keyword><keyword>Carrier Proteins/*metabolism</keyword><keyword>Cell Line</keyword><keyword>DNA Mutational Analysis</keyword><keyword>DNA, Complementary/metabolism</keyword><keyword>Fibroblasts/metabolism</keyword><keyword>Humans</keyword><keyword>*Membrane Proteins</keyword><keyword>Mitochondria/metabolism</keyword><keyword>Models, Biological</keyword><keyword>Neurons/cytology</keyword><keyword>Phosphorylation</keyword><keyword>Plasmids/metabolism</keyword><keyword>Protein Binding</keyword><keyword>Protein Isoforms</keyword><keyword>Proto-Oncogene Proteins/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-bcl-2/*metabolism</keyword><keyword>Signal Transduction</keyword><keyword>Threonine/chemistry</keyword><keyword>bcl-2-Associated X Protein</keyword></keywords><dates><year>2003</year><pub-dates><date>Mar 4</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>12591950</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12591950</url></related-urls></urls><custom2>151358</custom2><electronic-resource-num>10.1073/pnas.0438011100</electronic-resource-num></record></Cite><Cite><Author>Putcha</Author><Year>2003</Year><RecNum>580</RecNum><record><rec-number>580</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">580</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Putcha, G. V.</author><author>Le, S.</author><author>Frank, S.</author><author>Besirli, C. G.</author><author>Clark, K.</author><author>Chu, B.</author><author>Alix, S.</author><author>Youle, R. J.</author><author>LaMarche, A.</author><author>Maroney, A. C.</author><author>Johnson, E. M., Jr.</author></authors></contributors><auth-address>Department of Neurology and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Saint Louis, MO 63110, USA.</auth-address><titles><title>JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis</title><secondary-title>Neuron</secondary-title><alt-title>Neuron</alt-title></titles><periodical><full-title>Neuron</full-title><abbr-1>Neuron</abbr-1></periodical><alt-periodical><full-title>Neuron</full-title><abbr-1>Neuron</abbr-1></alt-periodical><pages>899-914</pages><volume>38</volume><number>6</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>*Apoptosis</keyword><keyword>Apoptosis Regulatory Proteins</keyword><keyword>Bcl-2-Like Protein 11</keyword><keyword>Carrier Proteins/chemistry/genetics/*physiology</keyword><keyword>Cells, Cultured</keyword><keyword>Cerebellum</keyword><keyword>Enzyme Activation</keyword><keyword>Gene Expression Regulation</keyword><keyword>Immune Sera/pharmacology</keyword><keyword>*JNK Mitogen-Activated Protein Kinases</keyword><keyword>MAP Kinase Kinase 4</keyword><keyword>*Membrane Proteins</keyword><keyword>Mice</keyword><keyword>Mitochondria/enzymology</keyword><keyword>Mitogen-Activated Protein Kinase Kinases/*metabolism</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutagenesis</keyword><keyword>Nerve Growth Factor/immunology/physiology</keyword><keyword>Neurons/*physiology</keyword><keyword>Phosphorylation</keyword><keyword>Protein Processing, Post-Translational</keyword><keyword>Proto-Oncogene Proteins/*physiology</keyword><keyword>*Proto-Oncogene Proteins c-bcl-2</keyword><keyword>Rats</keyword><keyword>Serine/genetics</keyword><keyword>Signal Transduction</keyword><keyword>Structure-Activity Relationship</keyword><keyword>Superior Cervical Ganglion</keyword><keyword>Transfection</keyword><keyword>bcl-2-Associated X Protein</keyword></keywords><dates><year>2003</year><pub-dates><date>Jun 19</date></pub-dates></dates><isbn>0896-6273 (Print)&#xD;0896-6273 (Linking)</isbn><accession-num>12818176</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12818176</url></related-urls></urls></record></Cite><Cite><Author>Luciano</Author><Year>2003</Year><RecNum>581</RecNum><record><rec-number>581</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">581</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Luciano, F.</author><author>Jacquel, A.</author><author>Colosetti, P.</author><author>Herrant, M.</author><author>Cagnol, S.</author><author>Pages, G.</author><author>Auberger, P.</author></authors></contributors><auth-address>INSERM Unit 526, LNC Label, Faculte de Medecine, 28 Avenue de Valombrose, 06107 Nice Cedex 02, France.</auth-address><titles><title>Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function</title><secondary-title>Oncogene</secondary-title><alt-title>Oncogene</alt-title></titles><periodical><full-title>Oncogene</full-title><abbr-1>Oncogene</abbr-1></periodical><alt-periodical><full-title>Oncogene</full-title><abbr-1>Oncogene</abbr-1></alt-periodical><pages>6785-93</pages><volume>22</volume><number>43</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Antineoplastic Agents, Hormonal/pharmacology</keyword><keyword>*Apoptosis</keyword><keyword>Apoptosis Regulatory Proteins</keyword><keyword>Bcl-2-Like Protein 11</keyword><keyword>Binding Sites</keyword><keyword>Carrier Proteins/*chemistry/*metabolism</keyword><keyword>Caspases/metabolism</keyword><keyword>Cell Line</keyword><keyword>Cell Survival</keyword><keyword>Cysteine Endopeptidases/*metabolism</keyword><keyword>Gene Expression Regulation</keyword><keyword>Glutathione Transferase/metabolism</keyword><keyword>Humans</keyword><keyword>K562 Cells</keyword><keyword>Lymphoma/metabolism</keyword><keyword>*Membrane Proteins</keyword><keyword>Mitogen-Activated Protein Kinase 1/*metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 3</keyword><keyword>Mitogen-Activated Protein Kinases/*metabolism</keyword><keyword>Models, Biological</keyword><keyword>Molecular Sequence Data</keyword><keyword>Multienzyme Complexes/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Proteasome Endopeptidase Complex</keyword><keyword>Protein Isoforms</keyword><keyword>*Proto-Oncogene Proteins</keyword><keyword>Proto-Oncogene Proteins c-raf/metabolism</keyword><keyword>Serine/*chemistry</keyword><keyword>Tamoxifen/pharmacology</keyword><keyword>Tetradecanoylphorbol Acetate</keyword><keyword>Time Factors</keyword><keyword>Transfection</keyword><keyword>Tumor Cells, Cultured</keyword></keywords><dates><year>2003</year><pub-dates><date>Oct 2</date></pub-dates></dates><isbn>0950-9232 (Print)&#xD;0950-9232 (Linking)</isbn><accession-num>14555991</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14555991</url></related-urls></urls><electronic-resource-num>10.1038/sj.onc.1206792</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Lei</Author><Year>2003</Year><RecNum>579</RecNum><DisplayText>[274-276]</DisplayText><record><rec-number>579</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">579</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lei, K.</author><author>Davis, R. J.</author></authors></contributors><auth-address>Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.</auth-address><titles><title>JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title><alt-title>Proceedings of the National Academy of Sciences of the United States of America</alt-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></periodical><alt-periodical><full-title>Proc Natl Acad Sci U S A</full-title><abbr-1>Proceedings of the National Academy of Sciences of the United States of America</abbr-1></alt-periodical><pages>2432-7</pages><volume>100</volume><number>5</number><keywords><keyword>*Adaptor Proteins, Signal Transducing</keyword><keyword>*Apoptosis</keyword><keyword>Apoptosis Regulatory Proteins</keyword><keyword>Bcl-2-Like Protein 11</keyword><keyword>Carrier Proteins/*metabolism</keyword><keyword>Cell Line</keyword><keyword>DNA Mutational Analysis</keyword><keyword>DNA, Complementary/metabolism</keyword><keyword>Fibroblasts/metabolism</keyword><keyword>Humans</keyword><keyword>*Membrane Proteins</keyword><keyword>Mitochondria/metabolism</keyword><keyword>Models, Biological</keyword><keyword>Neurons/cytology</keyword><keyword>Phosphorylation</keyword><keyword>Plasmids/metabolism</keyword><keyword>Protein Binding</keyword><keyword>Protein Isoforms</keyword><keyword>Proto-Oncogene Proteins/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-bcl-2/*metabolism</keyword><keyword>Signal Transduction</keyword><keyword>Threonine/chemistry</keyword><keyword>bcl-2-Associated X Protein</keyword></keywords><dates><year>2003</year><pub-dates><date>Mar 4</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>12591950</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12591950</url></related-urls></urls><custom2>151358</custom2><electronic-resource-num>10.1073/pnas.0438011100</electronic-resource-num></record></Cite><Cite><Author>Putcha</Author><Year>2003</Year><RecNum>580</RecNum><record><rec-number>580</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">580</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Putcha, G. V.</author><author>Le, S.</author><author>Frank, S.</author><author>Besirli, C. G.</author><author>Clark, K.</author><author>Chu, B.</author><author>Alix, S.</author><author>Youle, R. J.</author><author>LaMarche, A.</author><author>Maroney, A. C.</author><author>Johnson, E. M., Jr.</author></authors></contributors><auth-address>Department of Neurology and Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Saint Louis, MO 63110, USA.</auth-address><titles><title>JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis</title><secondary-title>Neuron</secondary-title><alt-title>Neuron</alt-title></titles><periodical><full-title>Neuron</full-title><abbr-1>Neuron</abbr-1></periodical><alt-periodical><full-title>Neuron</full-title><abbr-1>Neuron</abbr-1></alt-periodical><pages>899-914</pages><volume>38</volume><number>6</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>*Apoptosis</keyword><keyword>Apoptosis Regulatory Proteins</keyword><keyword>Bcl-2-Like Protein 11</keyword><keyword>Carrier Proteins/chemistry/genetics/*physiology</keyword><keyword>Cells, Cultured</keyword><keyword>Cerebellum</keyword><keyword>Enzyme Activation</keyword><keyword>Gene Expression Regulation</keyword><keyword>Immune Sera/pharmacology</keyword><keyword>*JNK Mitogen-Activated Protein Kinases</keyword><keyword>MAP Kinase Kinase 4</keyword><keyword>*Membrane Proteins</keyword><keyword>Mice</keyword><keyword>Mitochondria/enzymology</keyword><keyword>Mitogen-Activated Protein Kinase Kinases/*metabolism</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutagenesis</keyword><keyword>Nerve Growth Factor/immunology/physiology</keyword><keyword>Neurons/*physiology</keyword><keyword>Phosphorylation</keyword><keyword>Protein Processing, Post-Translational</keyword><keyword>Proto-Oncogene Proteins/*physiology</keyword><keyword>*Proto-Oncogene Proteins c-bcl-2</keyword><keyword>Rats</keyword><keyword>Serine/genetics</keyword><keyword>Signal Transduction</keyword><keyword>Structure-Activity Relationship</keyword><keyword>Superior Cervical Ganglion</keyword><keyword>Transfection</keyword><keyword>bcl-2-Associated X Protein</keyword></keywords><dates><year>2003</year><pub-dates><date>Jun 19</date></pub-dates></dates><isbn>0896-6273 (Print)&#xD;0896-6273 (Linking)</isbn><accession-num>12818176</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12818176</url></related-urls></urls></record></Cite><Cite><Author>Luciano</Author><Year>2003</Year><RecNum>581</RecNum><record><rec-number>581</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">581</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Luciano, F.</author><author>Jacquel, A.</author><author>Colosetti, P.</author><author>Herrant, M.</author><author>Cagnol, S.</author><author>Pages, G.</author><author>Auberger, P.</author></authors></contributors><auth-address>INSERM Unit 526, LNC Label, Faculte de Medecine, 28 Avenue de Valombrose, 06107 Nice Cedex 02, France.</auth-address><titles><title>Phosphorylation of Bim-EL by Erk1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function</title><secondary-title>Oncogene</secondary-title><alt-title>Oncogene</alt-title></titles><periodical><full-title>Oncogene</full-title><abbr-1>Oncogene</abbr-1></periodical><alt-periodical><full-title>Oncogene</full-title><abbr-1>Oncogene</abbr-1></alt-periodical><pages>6785-93</pages><volume>22</volume><number>43</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Antineoplastic Agents, Hormonal/pharmacology</keyword><keyword>*Apoptosis</keyword><keyword>Apoptosis Regulatory Proteins</keyword><keyword>Bcl-2-Like Protein 11</keyword><keyword>Binding Sites</keyword><keyword>Carrier Proteins/*chemistry/*metabolism</keyword><keyword>Caspases/metabolism</keyword><keyword>Cell Line</keyword><keyword>Cell Survival</keyword><keyword>Cysteine Endopeptidases/*metabolism</keyword><keyword>Gene Expression Regulation</keyword><keyword>Glutathione Transferase/metabolism</keyword><keyword>Humans</keyword><keyword>K562 Cells</keyword><keyword>Lymphoma/metabolism</keyword><keyword>*Membrane Proteins</keyword><keyword>Mitogen-Activated Protein Kinase 1/*metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 3</keyword><keyword>Mitogen-Activated Protein Kinases/*metabolism</keyword><keyword>Models, Biological</keyword><keyword>Molecular Sequence Data</keyword><keyword>Multienzyme Complexes/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Proteasome Endopeptidase Complex</keyword><keyword>Protein Isoforms</keyword><keyword>*Proto-Oncogene Proteins</keyword><keyword>Proto-Oncogene Proteins c-raf/metabolism</keyword><keyword>Serine/*chemistry</keyword><keyword>Tamoxifen/pharmacology</keyword><keyword>Tetradecanoylphorbol Acetate</keyword><keyword>Time Factors</keyword><keyword>Transfection</keyword><keyword>Tumor Cells, Cultured</keyword></keywords><dates><year>2003</year><pub-dates><date>Oct 2</date></pub-dates></dates><isbn>0950-9232 (Print)&#xD;0950-9232 (Linking)</isbn><accession-num>14555991</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14555991</url></related-urls></urls><electronic-resource-num>10.1038/sj.onc.1206792</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 274-276 while inhibiting anti-apoptotic Bcl-2 protein 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 277.1.6.ER stress and Type 2 diabetes:The UPR plays a critical role in re-establishment of cellular homeostasis; but, sustained or chronic stress can lead to different diseases like obesity, T2D, atherosclerosis, heart and liver diseases, and neurodegenerative disorders, among others 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 235, 278, making?ER?stress?an? instigator?of?pathological?cell death?and?dysfunction. Type 2 diabetes (T2D) is the most studied and widely explored metabolic disorder associated with ER stress. T2D is a chronic disease characterized by a combination of multiple disorders like peripheral insulin resistance, dysregulated hepatic glucose production, inadequate insulin secretion by pancreatic ?-cells and defective insulin signalling at the molecular level ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2004</Year><RecNum>334</RecNum><DisplayText>279</DisplayText><record><rec-number>334</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>334</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lee, Y. H.</author><author>White, M. F.</author></authors></contributors><auth-address>Institute for Tumor Research, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea.</auth-address><titles><title>Insulin receptor substrate proteins and diabetes</title><secondary-title>Arch Pharm Res</secondary-title><alt-title>Archives of pharmacal research</alt-title></titles><periodical><full-title>Arch Pharm Res</full-title><abbr-1>Archives of pharmacal research</abbr-1></periodical><alt-periodical><full-title>Arch Pharm Res</full-title><abbr-1>Archives of pharmacal research</abbr-1></alt-periodical><pages>361-70</pages><volume>27</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>Intracellular Signaling Peptides and Proteins</keyword><keyword>Phosphoproteins/*physiology</keyword><keyword>Receptor, Insulin/*physiology</keyword></keywords><dates><year>2004</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>0253-6269 (Print) 0253-6269 (Linking)</isbn><accession-num>15180298</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15180298</url></related-urls></urls></record></Cite></EndNote>279. Mice?lacking?PERK?are?susceptible?to?diabetes and display progressive ?-cell apoptosis?and 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ADDIN EN.CITE.DATA 280. Similarly, a mutation in human eIF2? kinase gene, EIF2AK3 (equivalent to rodent PERK) results in a truncated or missense eIF2? kinase with little or no activity 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ADDIN EN.CITE.DATA 281 and causes infant-onset?diabetes in?humans?with?the?autosomal?recessive?disorder?Wolcott-Rallison?syndrome? ADDIN EN.CITE <EndNote><Cite><Author>Araki</Author><Year>2003</Year><RecNum>584</RecNum><DisplayText>282</DisplayText><record><rec-number>584</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>584</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Araki, E.</author><author>Oyadomari, S.</author><author>Mori, M.</author></authors></contributors><auth-address>Department of Metabolic Medicine, Kumamoto University School of Medicine, Honjo Kumamoto 860-8556.</auth-address><titles><title>Endoplasmic reticulum stress and diabetes mellitus</title><secondary-title>Intern Med</secondary-title><alt-title>Internal medicine</alt-title></titles><periodical><full-title>Intern Med</full-title><abbr-1>Internal medicine</abbr-1></periodical><alt-periodical><full-title>Intern Med</full-title><abbr-1>Internal medicine</abbr-1></alt-periodical><pages>7-14</pages><volume>42</volume><number>1</number><keywords><keyword>Amyloid/metabolism</keyword><keyword>Animals</keyword><keyword>Apoptosis</keyword><keyword>Diabetes Mellitus/etiology/*metabolism/pathology</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Eukaryotic Initiation Factor-2/deficiency</keyword><keyword>Humans</keyword><keyword>Islets of Langerhans/metabolism/pathology</keyword><keyword>Mice</keyword><keyword>Mice, Mutant Strains</keyword><keyword>Models, Biological</keyword><keyword>Nitric Oxide/metabolism</keyword><keyword>Protein Folding</keyword><keyword>eIF-2 Kinase/deficiency</keyword></keywords><dates><year>2003</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0918-2918 (Print) 0918-2918 (Linking)</isbn><accession-num>12583611</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12583611</url></related-urls></urls></record></Cite></EndNote>282. On autopsy,?these?patients?show?massive???cell?loss,?resembling?the?pathology?of?perk–/–mice. Further, eIF2? (S51A)?knock-in?mice?showed acute ?-cell?depletion starting in?the utero 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 241, strengthening the importance of the PERK-mediated ER stress in ?-cell differentiation and proliferation for postnatal glucose homeostasis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 283. In addition, CHOP expression mediates ?-cells?apoptosis?induced?by?nitric oxide while, knockout of?CHOP in?rodent?models?of?diabetes delays?disease?onset 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 284, 285, further implicating?ER?stress?as?an?instigator?of??-cell?death.? In addition, to PERK, the ablation of ATF6? in INS-1 insulinoma cells demonstrates its importance in maintains ?-cells survival under chronic ER stress. ATF6? transcriptionally regulates the Wolfram syndrome 1 (WFS1) gene 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 286, mutations of which cause Wolfram syndrome, a genetic form of diabetes caused by non-autoimmune loss of ?-cells, whereas WFS1 polymorphisms are associated with T2D 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 287. ATF6 is also considered as a minor type 2 diabetes susceptibility gene in Pima Indians ADDIN EN.CITE <EndNote><Cite><Author>Thameem</Author><Year>2006</Year><RecNum>656</RecNum><DisplayText>288</DisplayText><record><rec-number>656</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>656</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Thameem, F.</author><author>Farook, V. S.</author><author>Bogardus, C.</author><author>Prochazka, M.</author></authors></contributors><auth-address>Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 445 N. 5th St., Suite 210, Phoenix, AZ 85004, USA.</auth-address><titles><title>Association of amino acid variants in the activating transcription factor 6 gene (ATF6) on 1q21-q23 with type 2 diabetes in Pima Indians</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>839-42</pages><volume>55</volume><number>3</number><keywords><keyword>Activating Transcription Factor 6/*genetics</keyword><keyword>Adult</keyword><keyword>*Chromosomes, Human, Pair 1</keyword><keyword>Diabetes Mellitus, Type 2/*genetics</keyword><keyword>Humans</keyword><keyword>Indians, North American/*genetics</keyword><keyword>*Polymorphism, Single Nucleotide</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0012-1797 (Print) 0012-1797 (Linking)</isbn><accession-num>16505252</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16505252</url></related-urls></urls></record></Cite></EndNote>288. Further, xbp-1+/–?heterozygous?mice?are observed to be more?sensitive?to?diabetes?caused?by?obesity?and?high-fat?diet?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 ADDIN EN.CITE 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ADDIN EN.CITE.DATA 142 as XBP-1 is required for?reducing?JNK?activation?caused?by?ER?stress,?thus inhibiting Ser phosphorylation of IRS1.?Further, observations such as intense staining of BiP, CHOP, and p58IPK 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 ADDIN EN.CITE 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ADDIN EN.CITE.DATA 289 and enlarged ER (2-fold increase) 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ADDIN EN.CITE.DATA 290 in ?-cells of T2D patients compared with non-diabetic counterparts provided direct evidence for the involvement of ER stress in T2D. Huang et al. recently reported an increased expression of CHOP, predominantly cytoplasmic, in ?-cells of obese subjects, unrelated to diabetes, while nuclear localization of CHOP was frequent in the pancreatic sections of diabetic patients 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 291, speculating nuclear translocation CHOP as a discrete and necessary step for induction of apoptosis. Additional, islets isolated from T2D organ donors induced BiP and XBP1 expression significantly at 11mM glucose compared with control islets but did not show any change in ER stress markers at 5mM glucose concentration of glucose 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 290.1.6.1.ER stress-mediated insulin resistance in various tissues:One of the preliminary factors that cause T2D is insulin resistance. As discussed earlier several factors lead to the state of insulin resistance among them ER stress is one. ER stress on itself or in association with dyslipidemia, hyperglycemia and chronic state of inflammation promotes insulin resistance leading to obesity and T2D. ER stress in obese mice was first observed in 2006, and it was proposed as a risk factor for insulin resistance 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ADDIN EN.CITE.DATA 218. As with other signal transduction pathways, the signal elicited by the UPR causing insulin resistance depends on the cell type and stimulus.1.6.1.a.Hypothalamus:Hypothalamic ER stress provides the molecular link to local inflammation and obesity that can lead to insulin resistance <EndNote><Cite><Author>Milanski</Author><Year>2009</Year><RecNum>586</RecNum><DisplayText>[292-294]</DisplayText><record><rec-number>586</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">586</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Milanski, M.</author><author>Degasperi, G.</author><author>Coope, A.</author><author>Morari, J.</author><author>Denis, R.</author><author>Cintra, D. E.</author><author>Tsukumo, D. M.</author><author>Anhe, G.</author><author>Amaral, M. E.</author><author>Takahashi, H. K.</author><author>Curi, R.</author><author>Oliveira, H. C.</author><author>Carvalheira, J. B.</author><author>Bordin, S.</author><author>Saad, M. J.</author><author>Velloso, L. A.</author></authors></contributors><auth-address>Department of Internal Medicine , Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.</auth-address><titles><title>Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity</title><secondary-title>J Neurosci</secondary-title><alt-title>The Journal of neuroscience : the official journal of the Society for Neuroscience</alt-title></titles><periodical><full-title>J Neurosci</full-title><abbr-1>The Journal of neuroscience : the official journal of the Society for Neuroscience</abbr-1></periodical><alt-periodical><full-title>J Neurosci</full-title><abbr-1>The Journal of neuroscience : the official journal of the Society for Neuroscience</abbr-1></alt-periodical><pages>359-70</pages><volume>29</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Antibodies/administration &amp; dosage</keyword><keyword>Body Weight/drug effects</keyword><keyword>Cytokines/classification/genetics/*metabolism</keyword><keyword>Disease Models, Animal</keyword><keyword>Fatty Acids/*administration &amp; dosage</keyword><keyword>Gene Expression Regulation/drug effects/physiology</keyword><keyword>Hypothalamus/drug effects/*metabolism</keyword><keyword>Immunoprecipitation</keyword><keyword>Indoles</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C3H</keyword><keyword>Mice, Mutant Strains</keyword><keyword>Microglia/drug effects</keyword><keyword>Mutation</keyword><keyword>Obesity/*chemically induced/immunology/metabolism/*pathology</keyword><keyword>RNA, Messenger/metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Signal Transduction/*drug effects</keyword><keyword>Toll-Like Receptor 2/immunology</keyword><keyword>Toll-Like Receptor 4/genetics/immunology/*metabolism</keyword></keywords><dates><year>2009</year><pub-dates><date>Jan 14</date></pub-dates></dates><isbn>1529-2401 (Electronic)&#xD;0270-6474 (Linking)</isbn><accession-num>19144836</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19144836</url></related-urls></urls><electronic-resource-num>10.1523/JNEUROSCI.2760-08.2009</electronic-resource-num></record></Cite><Cite><Author>Ozcan</Author><Year>2009</Year><RecNum>587</RecNum><record><rec-number>587</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">587</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozcan, L.</author><author>Ergin, A. S.</author><author>Lu, A.</author><author>Chung, J.</author><author>Sarkar, S.</author><author>Nie, D.</author><author>Myers, M. G., Jr.</author><author>Ozcan, U.</author></authors></contributors><auth-address>Division of Endocrinology, Children&apos;s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.</auth-address><titles><title>Endoplasmic reticulum stress plays a central role in development of leptin resistance</title><secondary-title>Cell Metab</secondary-title><alt-title>Cell metabolism</alt-title></titles><periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></periodical><alt-periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></alt-periodical><pages>35-51</pages><volume>9</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Endoplasmic Reticulum/drug effects/*metabolism</keyword><keyword>Hypothalamus/physiology</keyword><keyword>Leptin/pharmacology/*physiology</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Obese</keyword><keyword>Obesity/etiology</keyword><keyword>Phenylbutyrates/pharmacology</keyword><keyword>Receptors, Leptin/metabolism</keyword><keyword>Signal Transduction</keyword><keyword>Taurochenodeoxycholic Acid/pharmacology</keyword><keyword>Tunicamycin/pharmacology</keyword></keywords><dates><year>2009</year><pub-dates><date>Jan 7</date></pub-dates></dates><isbn>1932-7420 (Electronic)&#xD;1550-4131 (Linking)</isbn><accession-num>19117545</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19117545</url></related-urls></urls><electronic-resource-num>10.1016/j.cmet.2008.12.004</electronic-resource-num></record></Cite><Cite><Author>Zhang</Author><Year>2008</Year><RecNum>588</RecNum><record><rec-number>588</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">588</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhang, X.</author><author>Zhang, G.</author><author>Zhang, H.</author><author>Karin, M.</author><author>Bai, H.</author><author>Cai, D.</author></authors></contributors><auth-address>Department of Physiology, University of Wisconsin-Madison, Madison, WI 53706, USA.</auth-address><titles><title>Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>61-73</pages><volume>135</volume><number>1</number><keywords><keyword>Agouti-Related Protein/genetics/metabolism</keyword><keyword>Animals</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>*Energy Metabolism</keyword><keyword>Humans</keyword><keyword>Hypothalamus/immunology/*physiopathology</keyword><keyword>I-kappa B Proteins/*metabolism</keyword><keyword>Immunity, Innate</keyword><keyword>Insulin Resistance</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>NF-kappa B/*metabolism</keyword><keyword>Neurons/metabolism</keyword><keyword>Obesity/metabolism</keyword><keyword>Overnutrition/*physiopathology</keyword><keyword>*Signal Transduction</keyword><keyword>Suppressor of Cytokine Signaling 3 Protein</keyword><keyword>Suppressor of Cytokine Signaling Proteins/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Oct 3</date></pub-dates></dates><isbn>1097-4172 (Electronic)&#xD;0092-8674 (Linking)</isbn><accession-num>18854155</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18854155</url></related-urls></urls><custom2>2586330</custom2><electronic-resource-num>10.1016/j.cell.2008.07.043</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Milanski</Author><Year>2009</Year><RecNum>586</RecNum><DisplayText>[292-294]</DisplayText><record><rec-number>586</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">586</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Milanski, M.</author><author>Degasperi, G.</author><author>Coope, A.</author><author>Morari, J.</author><author>Denis, R.</author><author>Cintra, D. E.</author><author>Tsukumo, D. M.</author><author>Anhe, G.</author><author>Amaral, M. E.</author><author>Takahashi, H. K.</author><author>Curi, R.</author><author>Oliveira, H. C.</author><author>Carvalheira, J. B.</author><author>Bordin, S.</author><author>Saad, M. J.</author><author>Velloso, L. A.</author></authors></contributors><auth-address>Department of Internal Medicine , Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.</auth-address><titles><title>Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity</title><secondary-title>J Neurosci</secondary-title><alt-title>The Journal of neuroscience : the official journal of the Society for Neuroscience</alt-title></titles><periodical><full-title>J Neurosci</full-title><abbr-1>The Journal of neuroscience : the official journal of the Society for Neuroscience</abbr-1></periodical><alt-periodical><full-title>J Neurosci</full-title><abbr-1>The Journal of neuroscience : the official journal of the Society for Neuroscience</abbr-1></alt-periodical><pages>359-70</pages><volume>29</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Antibodies/administration &amp; dosage</keyword><keyword>Body Weight/drug effects</keyword><keyword>Cytokines/classification/genetics/*metabolism</keyword><keyword>Disease Models, Animal</keyword><keyword>Fatty Acids/*administration &amp; dosage</keyword><keyword>Gene Expression Regulation/drug effects/physiology</keyword><keyword>Hypothalamus/drug effects/*metabolism</keyword><keyword>Immunoprecipitation</keyword><keyword>Indoles</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C3H</keyword><keyword>Mice, Mutant Strains</keyword><keyword>Microglia/drug effects</keyword><keyword>Mutation</keyword><keyword>Obesity/*chemically induced/immunology/metabolism/*pathology</keyword><keyword>RNA, Messenger/metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Signal Transduction/*drug effects</keyword><keyword>Toll-Like Receptor 2/immunology</keyword><keyword>Toll-Like Receptor 4/genetics/immunology/*metabolism</keyword></keywords><dates><year>2009</year><pub-dates><date>Jan 14</date></pub-dates></dates><isbn>1529-2401 (Electronic)&#xD;0270-6474 (Linking)</isbn><accession-num>19144836</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19144836</url></related-urls></urls><electronic-resource-num>10.1523/JNEUROSCI.2760-08.2009</electronic-resource-num></record></Cite><Cite><Author>Ozcan</Author><Year>2009</Year><RecNum>587</RecNum><record><rec-number>587</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">587</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozcan, L.</author><author>Ergin, A. S.</author><author>Lu, A.</author><author>Chung, J.</author><author>Sarkar, S.</author><author>Nie, D.</author><author>Myers, M. G., Jr.</author><author>Ozcan, U.</author></authors></contributors><auth-address>Division of Endocrinology, Children&apos;s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.</auth-address><titles><title>Endoplasmic reticulum stress plays a central role in development of leptin resistance</title><secondary-title>Cell Metab</secondary-title><alt-title>Cell metabolism</alt-title></titles><periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></periodical><alt-periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></alt-periodical><pages>35-51</pages><volume>9</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Endoplasmic Reticulum/drug effects/*metabolism</keyword><keyword>Hypothalamus/physiology</keyword><keyword>Leptin/pharmacology/*physiology</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Obese</keyword><keyword>Obesity/etiology</keyword><keyword>Phenylbutyrates/pharmacology</keyword><keyword>Receptors, Leptin/metabolism</keyword><keyword>Signal Transduction</keyword><keyword>Taurochenodeoxycholic Acid/pharmacology</keyword><keyword>Tunicamycin/pharmacology</keyword></keywords><dates><year>2009</year><pub-dates><date>Jan 7</date></pub-dates></dates><isbn>1932-7420 (Electronic)&#xD;1550-4131 (Linking)</isbn><accession-num>19117545</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19117545</url></related-urls></urls><electronic-resource-num>10.1016/j.cmet.2008.12.004</electronic-resource-num></record></Cite><Cite><Author>Zhang</Author><Year>2008</Year><RecNum>588</RecNum><record><rec-number>588</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">588</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhang, X.</author><author>Zhang, G.</author><author>Zhang, H.</author><author>Karin, M.</author><author>Bai, H.</author><author>Cai, D.</author></authors></contributors><auth-address>Department of Physiology, University of Wisconsin-Madison, Madison, WI 53706, USA.</auth-address><titles><title>Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>61-73</pages><volume>135</volume><number>1</number><keywords><keyword>Agouti-Related Protein/genetics/metabolism</keyword><keyword>Animals</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>*Energy Metabolism</keyword><keyword>Humans</keyword><keyword>Hypothalamus/immunology/*physiopathology</keyword><keyword>I-kappa B Proteins/*metabolism</keyword><keyword>Immunity, Innate</keyword><keyword>Insulin Resistance</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>NF-kappa B/*metabolism</keyword><keyword>Neurons/metabolism</keyword><keyword>Obesity/metabolism</keyword><keyword>Overnutrition/*physiopathology</keyword><keyword>*Signal Transduction</keyword><keyword>Suppressor of Cytokine Signaling 3 Protein</keyword><keyword>Suppressor of Cytokine Signaling Proteins/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Oct 3</date></pub-dates></dates><isbn>1097-4172 (Electronic)&#xD;0092-8674 (Linking)</isbn><accession-num>18854155</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18854155</url></related-urls></urls><custom2>2586330</custom2><electronic-resource-num>10.1016/j.cell.2008.07.043</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 292-294. Treatment with chemical chaperones suppresses ER stress-activated IKK/NF?B pathway and protects from leptin resistance 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 293. However, functional implication of ER stress-induced hypothalamic insulin resistance is still unclear. Exposure of FFAs to freshly isolated hypothalamic neuronal cells induced ER stress 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 295 but failed to cause inflammation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 296; however genetic tailoring or chemically induced ER stress in the hypothalamus of rodents developed inflammations, leptin resistance and increased caloric intake 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 293. Conversely, relieving ER stress in the hypothalamus of obese mice enhanced leptin sensitivity, but had minimal impact on adiposity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 292, 293. In DIO (Diet induced obesity) mice, knockdown of TLR4 relieved hypothalamic ER stress and reduced adiposity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 292. Further, obese mice upon physical endurance test displayed inhibition of hypothalamic PERK due to upregulation of anti-inflammatory signalling (IL-6 and IL-10) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 297. Collectively, ER dysfunction in the hypothalamus of obese rodents is modulated by inflammatory signalling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 298. Importantly, elevating ER stress in hypothalamus partially rescues leptin resistance but fails to display significant changes in adiposity.1.6.1.b.Adipose tissue:Obesity-induced macrophage polarization is the primary cause of ER stress in fat depots . Nonesterified fatty acids (NEFAs) released from the visceral adipose tissue of obese subjects trigger the release of pro-inflammatory cytokines such as TNF-? and IL-6 by activation of NF-kB pathway 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 299. This increase in cytokine expression along with free fatty acid insults helps in further aggravating ER stress and developing insulin resistance. Exposure to lipopolysaccharide (due to leaky gut) or high glucose/lipid levels potentiates the ATF-6 and IRE-1?-dependent chaperone expression in human adipocytes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 300. Consistently, hyperactivation of IRE-1, JNK, and upregulation of XBP1s expression is observed in adipose tissue from obese patients 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 301. Thus, loss of fat in obese patients following gastric bypass surgery reduces XBP1s and BiP expression in white adipose tissue, as well as the phosphorylation levels of eIF2? and JNK 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ADDIN EN.CITE.DATA 146 and improving insulin sensitivity. In addition, physical endurance like training also decreases ER stress and IR in the white adipose tissue of obese rodents 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 302. ER stress promotes accumulation of intracellular fatty acids via inhibition of Perilipin A resulting in lipolysis of TG in adipocytes and uptake of very low-density lipoproteins (VLDLs) through the VLDL receptor (VLDLR) that leads to inflammation and metabolic dysfunction during obesity. Thus, deficiency of VLDLR restricts HFD induced lipid accumulation, inflammation, and ER stress in adipose tissue, in conjunction with reduced macrophage infiltration 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 303. Finally, ER stress induces thioredoxin-interacting protein (TXNIP) expression, which inhibits glucose uptake in fat and muscle 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 304 and is strongly induced proteins in diabetic patients 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 228.1.6.1.c.Liver:ER stress contributes to hepatic IR by up-regulating gluconeogenesis and increased lipogenesis . ER stress activates a liver-specific ATF6 homolog, cAMP-response element-binding protein H (CREBH), which enhances the expression of gluconeogenic genes like phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), along with inflammatory markers such as C-reactive protein (CRP) to induce insulin resistance. However, overexpression of XBP1s suppresses gluconeogenesis by inducing proteasomal degradation of FoxO1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 305.Increased lipogenesis also plays a pivotal role in ER stress to cause IR and hepatic steatosis specifically, through the accumulation of DAG 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 306. HepG2 cells exposed to hyperglycemia or saturated fatty acids like palmitate or the liver of obese rodents show PERK–eIF2a mediated transcriptional activation of sterol regulatory element binding protein (SREBP)-1 that enhances the transcription of lipogenic genes including fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD)1 leading to lipid accumulation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 307, 308. PERK–eIF2a pathway can also result in the increased expression of hepatic VLDLR, through the transcriptional activity of ATF4, to promote lipoprotein delivery to the liver 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 309. In addition, the IRE-1?–XBP1 pathway can also activate SREBP-1c by rapid degradation of its upstream inhibitor insulin-induced gene 1 (Insig1) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 310 and direct transcriptional activation of the SREBP-1c gene 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 311. However, some authors support the hypothesis that fat accumulation per se does not induce insulin resistance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 312. For instance, CHOP knockout mice displayed normal glucose tolerance and insulin sensitivity despite marked obesity due to diminished inflammation in adipose and liver of knockout mice, thus reinforcing the idea that insulin resistance is not induced by fat accumulation by itself, but rather a collective disorder 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 312.1.6.1.d.Pancreatic ? cells:The UPR behaves like a binary switch between life and death in ?-cells. A mild ER stress (e.g. physiological exposure to glucose fluctuations following a meal), promotes insulin production by activation of UPR pro-survival pathways, while unresolvable ER stress (e.g, genetic mutations, lipotoxicity, glucotoxicity, inflammatory challenge, and the accumulation of proinsulin and amyloid, as well as dysregulation of the UPR itself, leads to ?-cell dysfunction and apoptosis ADDIN EN.CITE <EndNote><Cite><Author>Eizirik</Author><Year>2010</Year><RecNum>628</RecNum><DisplayText>313</DisplayText><record><rec-number>628</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>628</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Eizirik, D. L.</author><author>Cnop, M.</author></authors></contributors><auth-address>Laboratory of Experimental Medicine, Universite Libre de Bruxelles (ULB), 1070 Brussels, Belgium. [email protected]</auth-address><titles><title>ER stress in pancreatic beta cells: the thin red line between adaptation and failure</title><secondary-title>Sci Signal</secondary-title><alt-title>Science signaling</alt-title></titles><periodical><full-title>Sci Signal</full-title><abbr-1>Science signaling</abbr-1></periodical><alt-periodical><full-title>Sci Signal</full-title><abbr-1>Science signaling</abbr-1></alt-periodical><pages>pe7</pages><volume>3</volume><number>110</number><keywords><keyword>Adaptation, Biological/*physiology</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Humans</keyword><keyword>Insulin-Secreting Cells/*physiology</keyword><keyword>Signal Transduction/*physiology</keyword><keyword>Stress, Physiological/*physiology</keyword><keyword>Unfolded Protein Response/*physiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Feb 23</date></pub-dates></dates><isbn>1937-9145 (Electronic) 1945-0877 (Linking)</isbn><accession-num>20179270</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20179270</url></related-urls></urls><electronic-resource-num>10.1126/scisignal.3110pe7</electronic-resource-num></record></Cite></EndNote>313. Hyperglycemia/glucotoxicity leads to increased insulin biosynthesis that can overwhelm the ER folding capacity, causing an imbalance in ER homeostasis resulting in ER stress. Acute state of high glucose (1–3 hours) transiently activates IRE1? to enhance proinsulin biosynthesis, while chronic high glucose state (? 24 hours) leads to prolonged activation of IRE1? that leads to induction of pro-apoptotic effectors, such as JNK and CHOP causing ? cell dysfunction and death <EndNote><Cite><Author>Elouil</Author><Year>2007</Year><RecNum>608</RecNum><DisplayText>[314-317]</DisplayText><record><rec-number>608</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">608</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Elouil, H.</author><author>Bensellam, M.</author><author>Guiot, Y.</author><author>Vander Mierde, D.</author><author>Pascal, S. M.</author><author>Schuit, F. C.</author><author>Jonas, J. C.</author></authors></contributors><auth-address>Unit of Endocrinology and Metabolism, Faculty of Medicine, Universite Catholique de Louvain, Avenue Hippocrate, 55 (UCL 55.30), 1200, Brussels, Belgium.</auth-address><titles><title>Acute nutrient regulation of the unfolded protein response and integrated stress response in cultured rat pancreatic islets</title><secondary-title>Diabetologia</secondary-title><alt-title>Diabetologia</alt-title></titles><periodical><full-title>Diabetologia</full-title><abbr-1>Diabetologia</abbr-1></periodical><alt-periodical><full-title>Diabetologia</full-title><abbr-1>Diabetologia</abbr-1></alt-periodical><pages>1442-52</pages><volume>50</volume><number>7</number><keywords><keyword>Alternative Splicing</keyword><keyword>Animals</keyword><keyword>Calcium/metabolism</keyword><keyword>Culture Media/metabolism</keyword><keyword>Cycloheximide/pharmacology</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Insulin/secretion</keyword><keyword>Insulin-Secreting Cells/*metabolism</keyword><keyword>Kinetics</keyword><keyword>Molecular Chaperones/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Synthesis Inhibitors/pharmacology</keyword><keyword>Rats</keyword><keyword>Thapsigargin/pharmacology</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0012-186X (Print)&#xD;0012-186X (Linking)</isbn><accession-num>17497122</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17497122</url></related-urls></urls><electronic-resource-num>10.1007/s00125-007-0674-4</electronic-resource-num></record></Cite><Cite><Author>Lipson</Author><Year>2006</Year><RecNum>609</RecNum><record><rec-number>609</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">609</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lipson, K. L.</author><author>Fonseca, S. G.</author><author>Ishigaki, S.</author><author>Nguyen, L. X.</author><author>Foss, E.</author><author>Bortell, R.</author><author>Rossini, A. A.</author><author>Urano, F.</author></authors></contributors><auth-address>Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.</auth-address><titles><title>Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1</title><secondary-title>Cell Metab</secondary-title><alt-title>Cell metabolism</alt-title></titles><periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></periodical><alt-periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></alt-periodical><pages>245-54</pages><volume>4</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Survival/physiology</keyword><keyword>DNA-Binding Proteins/genetics/metabolism</keyword><keyword>Down-Regulation/genetics</keyword><keyword>Endoplasmic Reticulum/*metabolism/secretion</keyword><keyword>Gene Expression Regulation/physiology</keyword><keyword>Glucose/*metabolism</keyword><keyword>Heat-Shock Proteins/genetics/metabolism</keyword><keyword>Hyperglycemia/metabolism/physiopathology</keyword><keyword>Insulin/*biosynthesis/secretion</keyword><keyword>Insulin-Secreting Cells/*metabolism/secretion</keyword><keyword>Membrane Proteins/genetics/*metabolism</keyword><keyword>Mice</keyword><keyword>Molecular Chaperones/genetics/metabolism</keyword><keyword>Nuclear Proteins/genetics/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Proinsulin/metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/genetics/*metabolism</keyword><keyword>RNA Interference</keyword><keyword>Rats</keyword><keyword>Regulatory Factor X Transcription Factors</keyword><keyword>Signal Transduction/physiology</keyword><keyword>Stress, Physiological/metabolism/physiopathology</keyword><keyword>Transcription Factors</keyword><keyword>Up-Regulation/physiology</keyword><keyword>X-Box Binding Protein 1</keyword></keywords><dates><year>2006</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1550-4131 (Print)&#xD;1550-4131 (Linking)</isbn><accession-num>16950141</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16950141</url></related-urls></urls><electronic-resource-num>10.1016/j.cmet.2006.07.007</electronic-resource-num></record></Cite><Cite><Author>Lipson</Author><Year>2008</Year><RecNum>610</RecNum><record><rec-number>610</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">610</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lipson, K. L.</author><author>Ghosh, R.</author><author>Urano, F.</author></authors></contributors><auth-address>Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts, USA.</auth-address><titles><title>The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells</title><secondary-title>PLoS One</secondary-title><alt-title>PloS one</alt-title></titles><periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></periodical><alt-periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></alt-periodical><pages>e1648</pages><volume>3</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Blood Glucose/physiology</keyword><keyword>Cells, Cultured</keyword><keyword>Endoribonucleases/*physiology</keyword><keyword>Insulin/*genetics</keyword><keyword>Insulin-Secreting Cells/*metabolism</keyword><keyword>Mice</keyword><keyword>Protein Folding</keyword><keyword>Protein-Serine-Threonine Kinases/*physiology</keyword><keyword>RNA, Messenger/*metabolism</keyword><keyword>Rats</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2008</year><pub-dates><date>Feb 20</date></pub-dates></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>18286202</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18286202</url></related-urls></urls><custom2>2241665</custom2><electronic-resource-num>10.1371/journal.pone.0001648</electronic-resource-num></record></Cite><Cite><Author>Jonas</Author><Year>2009</Year><RecNum>611</RecNum><record><rec-number>611</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">611</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jonas, J. C.</author><author>Bensellam, M.</author><author>Duprez, J.</author><author>Elouil, H.</author><author>Guiot, Y.</author><author>Pascal, S. M.</author></authors></contributors><auth-address>Universite catholique de Louvain, Brussels, Belgium. jean-christophe.jonas@uclouvain.be</auth-address><titles><title>Glucose regulation of islet stress responses and beta-cell failure in type 2 diabetes</title><secondary-title>Diabetes Obes Metab</secondary-title><alt-title>Diabetes, obesity &amp; metabolism</alt-title></titles><periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></periodical><alt-periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></alt-periodical><pages>65-81</pages><volume>11 Suppl 4</volume><keywords><keyword>Animals</keyword><keyword>Apoptosis/physiology</keyword><keyword>Cell Hypoxia/physiology</keyword><keyword>Diabetes Mellitus, Type 2/*physiopathology</keyword><keyword>Disease Progression</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Gene Expression</keyword><keyword>Glucose/*metabolism</keyword><keyword>Humans</keyword><keyword>Hyperglycemia/physiopathology</keyword><keyword>Hypoglycemia/physiopathology</keyword><keyword>Insulin-Secreting Cells/drug effects/*physiology</keyword><keyword>Oxidative Stress/*physiology</keyword><keyword>Rats</keyword></keywords><dates><year>2009</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1463-1326 (Electronic)&#xD;1462-8902 (Linking)</isbn><accession-num>19817790</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19817790</url></related-urls></urls><electronic-resource-num>10.1111/j.1463-1326.2009.01112.x</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Elouil</Author><Year>2007</Year><RecNum>608</RecNum><DisplayText>[314-317]</DisplayText><record><rec-number>608</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">608</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Elouil, H.</author><author>Bensellam, M.</author><author>Guiot, Y.</author><author>Vander Mierde, D.</author><author>Pascal, S. M.</author><author>Schuit, F. C.</author><author>Jonas, J. C.</author></authors></contributors><auth-address>Unit of Endocrinology and Metabolism, Faculty of Medicine, Universite Catholique de Louvain, Avenue Hippocrate, 55 (UCL 55.30), 1200, Brussels, Belgium.</auth-address><titles><title>Acute nutrient regulation of the unfolded protein response and integrated stress response in cultured rat pancreatic islets</title><secondary-title>Diabetologia</secondary-title><alt-title>Diabetologia</alt-title></titles><periodical><full-title>Diabetologia</full-title><abbr-1>Diabetologia</abbr-1></periodical><alt-periodical><full-title>Diabetologia</full-title><abbr-1>Diabetologia</abbr-1></alt-periodical><pages>1442-52</pages><volume>50</volume><number>7</number><keywords><keyword>Alternative Splicing</keyword><keyword>Animals</keyword><keyword>Calcium/metabolism</keyword><keyword>Culture Media/metabolism</keyword><keyword>Cycloheximide/pharmacology</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Insulin/secretion</keyword><keyword>Insulin-Secreting Cells/*metabolism</keyword><keyword>Kinetics</keyword><keyword>Molecular Chaperones/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Synthesis Inhibitors/pharmacology</keyword><keyword>Rats</keyword><keyword>Thapsigargin/pharmacology</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0012-186X (Print)&#xD;0012-186X (Linking)</isbn><accession-num>17497122</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17497122</url></related-urls></urls><electronic-resource-num>10.1007/s00125-007-0674-4</electronic-resource-num></record></Cite><Cite><Author>Lipson</Author><Year>2006</Year><RecNum>609</RecNum><record><rec-number>609</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">609</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lipson, K. L.</author><author>Fonseca, S. G.</author><author>Ishigaki, S.</author><author>Nguyen, L. X.</author><author>Foss, E.</author><author>Bortell, R.</author><author>Rossini, A. A.</author><author>Urano, F.</author></authors></contributors><auth-address>Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.</auth-address><titles><title>Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1</title><secondary-title>Cell Metab</secondary-title><alt-title>Cell metabolism</alt-title></titles><periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></periodical><alt-periodical><full-title>Cell Metab</full-title><abbr-1>Cell metabolism</abbr-1></alt-periodical><pages>245-54</pages><volume>4</volume><number>3</number><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Survival/physiology</keyword><keyword>DNA-Binding Proteins/genetics/metabolism</keyword><keyword>Down-Regulation/genetics</keyword><keyword>Endoplasmic Reticulum/*metabolism/secretion</keyword><keyword>Gene Expression Regulation/physiology</keyword><keyword>Glucose/*metabolism</keyword><keyword>Heat-Shock Proteins/genetics/metabolism</keyword><keyword>Hyperglycemia/metabolism/physiopathology</keyword><keyword>Insulin/*biosynthesis/secretion</keyword><keyword>Insulin-Secreting Cells/*metabolism/secretion</keyword><keyword>Membrane Proteins/genetics/*metabolism</keyword><keyword>Mice</keyword><keyword>Molecular Chaperones/genetics/metabolism</keyword><keyword>Nuclear Proteins/genetics/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Proinsulin/metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/genetics/*metabolism</keyword><keyword>RNA Interference</keyword><keyword>Rats</keyword><keyword>Regulatory Factor X Transcription Factors</keyword><keyword>Signal Transduction/physiology</keyword><keyword>Stress, Physiological/metabolism/physiopathology</keyword><keyword>Transcription Factors</keyword><keyword>Up-Regulation/physiology</keyword><keyword>X-Box Binding Protein 1</keyword></keywords><dates><year>2006</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1550-4131 (Print)&#xD;1550-4131 (Linking)</isbn><accession-num>16950141</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16950141</url></related-urls></urls><electronic-resource-num>10.1016/j.cmet.2006.07.007</electronic-resource-num></record></Cite><Cite><Author>Lipson</Author><Year>2008</Year><RecNum>610</RecNum><record><rec-number>610</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">610</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lipson, K. L.</author><author>Ghosh, R.</author><author>Urano, F.</author></authors></contributors><auth-address>Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts, USA.</auth-address><titles><title>The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells</title><secondary-title>PLoS One</secondary-title><alt-title>PloS one</alt-title></titles><periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></periodical><alt-periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></alt-periodical><pages>e1648</pages><volume>3</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>Blood Glucose/physiology</keyword><keyword>Cells, Cultured</keyword><keyword>Endoribonucleases/*physiology</keyword><keyword>Insulin/*genetics</keyword><keyword>Insulin-Secreting Cells/*metabolism</keyword><keyword>Mice</keyword><keyword>Protein Folding</keyword><keyword>Protein-Serine-Threonine Kinases/*physiology</keyword><keyword>RNA, Messenger/*metabolism</keyword><keyword>Rats</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2008</year><pub-dates><date>Feb 20</date></pub-dates></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>18286202</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18286202</url></related-urls></urls><custom2>2241665</custom2><electronic-resource-num>10.1371/journal.pone.0001648</electronic-resource-num></record></Cite><Cite><Author>Jonas</Author><Year>2009</Year><RecNum>611</RecNum><record><rec-number>611</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">611</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Jonas, J. C.</author><author>Bensellam, M.</author><author>Duprez, J.</author><author>Elouil, H.</author><author>Guiot, Y.</author><author>Pascal, S. M.</author></authors></contributors><auth-address>Universite catholique de Louvain, Brussels, Belgium. jean-christophe.jonas@uclouvain.be</auth-address><titles><title>Glucose regulation of islet stress responses and beta-cell failure in type 2 diabetes</title><secondary-title>Diabetes Obes Metab</secondary-title><alt-title>Diabetes, obesity &amp; metabolism</alt-title></titles><periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></periodical><alt-periodical><full-title>Diabetes Obes Metab</full-title><abbr-1>Diabetes, obesity &amp; metabolism</abbr-1></alt-periodical><pages>65-81</pages><volume>11 Suppl 4</volume><keywords><keyword>Animals</keyword><keyword>Apoptosis/physiology</keyword><keyword>Cell Hypoxia/physiology</keyword><keyword>Diabetes Mellitus, Type 2/*physiopathology</keyword><keyword>Disease Progression</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Gene Expression</keyword><keyword>Glucose/*metabolism</keyword><keyword>Humans</keyword><keyword>Hyperglycemia/physiopathology</keyword><keyword>Hypoglycemia/physiopathology</keyword><keyword>Insulin-Secreting Cells/drug effects/*physiology</keyword><keyword>Oxidative Stress/*physiology</keyword><keyword>Rats</keyword></keywords><dates><year>2009</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1463-1326 (Electronic)&#xD;1462-8902 (Linking)</isbn><accession-num>19817790</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19817790</url></related-urls></urls><electronic-resource-num>10.1111/j.1463-1326.2009.01112.x</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 314-317. Chronically elevated glucose also increases reactive oxygen species (ROS) which can also induce ER stress 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 318, 319. Upregulation of TRB3 in response to ER stress has been implicated in negative regulation of insulin exocytosis and ?-cell apoptosis in hyperglycemic rat islets 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 86, 320. Further, increased synthesis of proinsulin in response to hyperglycemia or hyperinsulinemic results in accumulation of misfolded proinsulin and toxic protein aggregates, called islet amyloid, formed by accumulations of misfolded human islet amyloid polypeptide (hIAPP) also activates the UPR which may culminate in ? cell apoptosis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 321.Lipotoxicity is one of the most important triggers of ER stress in pancreatic ? cells in human islets 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 322. Treatment of rodent islets with saturated fatty acids (e.g., palmitate) activate the PERK and IRE-1 pathways of the UPR, while, stimulations with monounsaturated fatty acids (e.g., oleate) reverse the adverse effects of palmitate and promotes protective effects against ?-cell apoptosis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 323, 324. Several factors contribute to ER stress-induced lipo-apoptosis such as increasing protein overload in the ER lumen due to reduces ER-to-Golgi trafficking 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 325, and upregulation of CHOP and activation of JNK and caspase-12 foremost to ?-cell death 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 326. Thus, reduction of ER stress by treatment with 4-phenylbutyrate (4-PBA) or forced expression of BiP partially prevented lipid-induced ?-cell dysfunction in overweight subjects 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 327 and protected mice against HFD-induced obesity and insulin resistance 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ADDIN EN.CITE.DATA 328, respectively.Inflammatory cytokines like IL-23, IL-24, and IL-33 also contributes to ER stress-mediated ?-cells apoptosis via activation of STATs and NF-?B pathway. Hence, neutralization of IL-23 or IL-24 partly improved ?-cell ER stress and glucose intolerance in obese mice; whereas, IL-22 administration suppressed ER stress as well as inflammation, and improved insulin secretion and restored insulin sensitivity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 329. ER, stress-mediated ?-cells failure is also associated with the Permanent neonatal diabetes or MIDY (Mutant INS-gene-induced Diabetes of Youth) where mutations in proinsulin resulted in the impairment of normal proinsulin folding and its accumulation in the ER lumen 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 330. Mouse models of this disease, the Munich and Akita exhibit progressive hyperglycemia associated with elevated levels of ER stress markers such as BiP and CHOP 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 331, 332, however, it remains controversial whether mutations alone is sufficient to activate apoptosis.1.6.1.e.Skeletal muscle:Skeletal muscle has a specialized form of ER known as sarcoplasmic reticulum (SR). The SR is a storage depot for calcium and regulates its release during myofibrillar contraction; hence, the SR has a critical role in muscle contraction and the maintenance of muscle homeostasis. In addition, skeletal muscle plays a prominent role in the regulation of body metabolism by modulating glucose uptake. Exposure of myogenic cell line (C2C12) to palmitic acid or feeding mice with HFD induced UPR by reduction of mTORC1 activity and upregulation of BiP, IRE1?, and membrane-bound transcription factor protease site 2 (MBTPS2) in the soleus and tibialis anterior muscles, respectively 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 333, 334. Further, acute stress, such as long-distance running, increases the expression of BiP and XBP1s in skeletal muscle was observed in muscle biopsies obtained from eight males before and after a 200-km run, indicating the importance of ER in skeletal muscle adaptation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 335. Further, PGC-1? mediates UPR in myotubes and skeletal muscle via the co-activation of ATF6? confirms the adaptive role of UPR in skeletal muscle to exercise using knockout mice 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 336. The potent chemical ER stressors, like tunicamycin and thapsigargin, can induce ER-stress in myotubes to promote insulin resistance through phosphorylation of IRS proteins via the IRE-1/JNK pathway 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 337 and by elevating the expression of the pseudokinase Trb3. Trb3 impair insulin signalling and glucose uptake in myotubes and mouse skeletal muscle while silencing Trb3 expression in cells and muscles specific Trb3 knockout in mice reverts the effects 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 87. However, the involvement of ER stress in lipid-induced muscle IR remains controversial. Few reports show that palmitate increases Trb3 expression, activates IRE1? signalling, and reduced the insulin-dependent Akt phosphorylation, but ablation of Trb3 or IRE1? did not prevent the inhibitory effect of palmitate on Akt phosphorylation.Further, the monounsaturated fatty acids like oleate, fail to induce ER stress in human and murine myotubes, prevented palmitate-induced ER stress, inflammation, and insulin resistance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 338 by activation of AMP-activated protein kinase (AMPK). AMPK exhibits multiple protective effects, including inhibition of inflammation, oxidative stress, and IR, besides attenuating ER stress <EndNote><Cite><Author>Terai</Author><Year>2005</Year><RecNum>375</RecNum><DisplayText>[339-341]</DisplayText><record><rec-number>375</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">375</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Terai, K.</author><author>Hiramoto, Y.</author><author>Masaki, M.</author><author>Sugiyama, S.</author><author>Kuroda, T.</author><author>Hori, M.</author><author>Kawase, I.</author><author>Hirota, H.</author></authors></contributors><auth-address>Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.</auth-address><titles><title>AMP-activated protein kinase protects cardiomyocytes against hypoxic injury through attenuation of endoplasmic reticulum stress</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>9554-75</pages><volume>25</volume><number>21</number><keywords><keyword>AMP-Activated Protein Kinases</keyword><keyword>Aminoimidazole Carboxamide/analogs &amp; derivatives/pharmacology</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Apoptosis</keyword><keyword>Calcium-Calmodulin-Dependent Protein Kinases/genetics</keyword><keyword>Caspase 12</keyword><keyword>Caspases/genetics/metabolism</keyword><keyword>Cell Hypoxia</keyword><keyword>Cells, Cultured</keyword><keyword>Elongation Factor 2 Kinase</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Enzyme Activation</keyword><keyword>Multienzyme Complexes/*physiology</keyword><keyword>Myocytes, Cardiac/metabolism/*physiology</keyword><keyword>Peptide Elongation Factor 2/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Poly(ADP-ribose) Polymerases/metabolism</keyword><keyword>Protein Folding</keyword><keyword>Protein-Serine-Threonine Kinases/*physiology</keyword><keyword>RNA, Small Interfering/genetics</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Ribonucleotides/pharmacology</keyword><keyword>Signal Transduction/physiology</keyword><keyword>Transcription Factor CHOP/metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>16227605</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16227605</url></related-urls></urls><custom2>1265833</custom2><electronic-resource-num>10.1128/MCB.25.21.9554-9575.2005</electronic-resource-num></record></Cite><Cite><Author>Dong</Author><Year>2010</Year><RecNum>663</RecNum><record><rec-number>663</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">663</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dong, Y.</author><author>Zhang, M.</author><author>Liang, B.</author><author>Xie, Z.</author><author>Zhao, Z.</author><author>Asfa, S.</author><author>Choi, H. C.</author><author>Zou, M. H.</author></authors></contributors><auth-address>Department of Medicine and Endocrinology, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.</auth-address><titles><title>Reduction of AMP-activated protein kinase alpha2 increases endoplasmic reticulum stress and atherosclerosis in vivo</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></periodical><alt-periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></alt-periodical><pages>792-803</pages><volume>121</volume><number>6</number><keywords><keyword>AMP-Activated Protein Kinases/genetics/*metabolism</keyword><keyword>Animals</keyword><keyword>Atherosclerosis/*metabolism/*physiopathology</keyword><keyword>Calcium/metabolism</keyword><keyword>Calcium-Calmodulin-Dependent Protein Kinases/metabolism</keyword><keyword>Cells, Cultured</keyword><keyword>Disease Models, Animal</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Endothelium, Vascular/cytology/metabolism</keyword><keyword>Homeostasis/physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Receptors, LDL/genetics/metabolism</keyword><keyword>Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism</keyword><keyword>Stress, Physiological/*physiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Feb 16</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>20124121</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20124121</url></related-urls></urls><custom2>2825900</custom2><electronic-resource-num>10.1161/CIRCULATIONAHA.109.900928</electronic-resource-num></record></Cite><Cite><Author>Wang</Author><Year>2011</Year><RecNum>664</RecNum><record><rec-number>664</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">664</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wang, Y.</author><author>Wu, Z.</author><author>Li, D.</author><author>Wang, D.</author><author>Wang, X.</author><author>Feng, X.</author><author>Xia, M.</author></authors></contributors><auth-address>Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, China.</auth-address><titles><title>Involvement of oxygen-regulated protein 150 in AMP-activated protein kinase-mediated alleviation of lipid-induced endoplasmic reticulum stress</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>11119-31</pages><volume>286</volume><number>13</number><keywords><keyword>AMP-Activated Protein Kinases/genetics/metabolism</keyword><keyword>Aminoimidazole Carboxamide/analogs &amp; derivatives/pharmacology</keyword><keyword>Animals</keyword><keyword>Apoptosis/drug effects/genetics</keyword><keyword>Endoplasmic Reticulum/genetics/*metabolism</keyword><keyword>Forkhead Box Protein O1</keyword><keyword>Forkhead Transcription Factors/genetics/metabolism</keyword><keyword>Gene Expression Regulation/drug effects/genetics</keyword><keyword>HSP70 Heat-Shock Proteins</keyword><keyword>Hep G2 Cells</keyword><keyword>Hepatocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Hypercholesterolemia/genetics/metabolism</keyword><keyword>Hypoglycemic Agents/pharmacology</keyword><keyword>Lipid Metabolism/*physiology</keyword><keyword>Liver Diseases/genetics/metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Proteins/genetics/*metabolism</keyword><keyword>Ribonucleotides/pharmacology</keyword><keyword>Sirtuin 1/genetics/metabolism</keyword><keyword>Unfolded Protein Response/drug effects/*physiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 1</date></pub-dates></dates><isbn>1083-351X (Electronic)&#xD;0021-9258 (Linking)</isbn><accession-num>21296878</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21296878</url></related-urls></urls><custom2>3064166</custom2><electronic-resource-num>10.1074/jbc.M110.203323</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Terai</Author><Year>2005</Year><RecNum>375</RecNum><DisplayText>[339-341]</DisplayText><record><rec-number>375</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">375</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Terai, K.</author><author>Hiramoto, Y.</author><author>Masaki, M.</author><author>Sugiyama, S.</author><author>Kuroda, T.</author><author>Hori, M.</author><author>Kawase, I.</author><author>Hirota, H.</author></authors></contributors><auth-address>Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.</auth-address><titles><title>AMP-activated protein kinase protects cardiomyocytes against hypoxic injury through attenuation of endoplasmic reticulum stress</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>9554-75</pages><volume>25</volume><number>21</number><keywords><keyword>AMP-Activated Protein Kinases</keyword><keyword>Aminoimidazole Carboxamide/analogs &amp; derivatives/pharmacology</keyword><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Apoptosis</keyword><keyword>Calcium-Calmodulin-Dependent Protein Kinases/genetics</keyword><keyword>Caspase 12</keyword><keyword>Caspases/genetics/metabolism</keyword><keyword>Cell Hypoxia</keyword><keyword>Cells, Cultured</keyword><keyword>Elongation Factor 2 Kinase</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Enzyme Activation</keyword><keyword>Multienzyme Complexes/*physiology</keyword><keyword>Myocytes, Cardiac/metabolism/*physiology</keyword><keyword>Peptide Elongation Factor 2/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Poly(ADP-ribose) Polymerases/metabolism</keyword><keyword>Protein Folding</keyword><keyword>Protein-Serine-Threonine Kinases/*physiology</keyword><keyword>RNA, Small Interfering/genetics</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Ribonucleotides/pharmacology</keyword><keyword>Signal Transduction/physiology</keyword><keyword>Transcription Factor CHOP/metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0270-7306 (Print)&#xD;0270-7306 (Linking)</isbn><accession-num>16227605</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16227605</url></related-urls></urls><custom2>1265833</custom2><electronic-resource-num>10.1128/MCB.25.21.9554-9575.2005</electronic-resource-num></record></Cite><Cite><Author>Dong</Author><Year>2010</Year><RecNum>663</RecNum><record><rec-number>663</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">663</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dong, Y.</author><author>Zhang, M.</author><author>Liang, B.</author><author>Xie, Z.</author><author>Zhao, Z.</author><author>Asfa, S.</author><author>Choi, H. C.</author><author>Zou, M. H.</author></authors></contributors><auth-address>Department of Medicine and Endocrinology, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.</auth-address><titles><title>Reduction of AMP-activated protein kinase alpha2 increases endoplasmic reticulum stress and atherosclerosis in vivo</title><secondary-title>Circulation</secondary-title><alt-title>Circulation</alt-title></titles><periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></periodical><alt-periodical><full-title>Circulation</full-title><abbr-1>Circulation</abbr-1></alt-periodical><pages>792-803</pages><volume>121</volume><number>6</number><keywords><keyword>AMP-Activated Protein Kinases/genetics/*metabolism</keyword><keyword>Animals</keyword><keyword>Atherosclerosis/*metabolism/*physiopathology</keyword><keyword>Calcium/metabolism</keyword><keyword>Calcium-Calmodulin-Dependent Protein Kinases/metabolism</keyword><keyword>Cells, Cultured</keyword><keyword>Disease Models, Animal</keyword><keyword>Endoplasmic Reticulum/*physiology</keyword><keyword>Endothelium, Vascular/cytology/metabolism</keyword><keyword>Homeostasis/physiology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Receptors, LDL/genetics/metabolism</keyword><keyword>Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism</keyword><keyword>Stress, Physiological/*physiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Feb 16</date></pub-dates></dates><isbn>1524-4539 (Electronic)&#xD;0009-7322 (Linking)</isbn><accession-num>20124121</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20124121</url></related-urls></urls><custom2>2825900</custom2><electronic-resource-num>10.1161/CIRCULATIONAHA.109.900928</electronic-resource-num></record></Cite><Cite><Author>Wang</Author><Year>2011</Year><RecNum>664</RecNum><record><rec-number>664</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">664</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wang, Y.</author><author>Wu, Z.</author><author>Li, D.</author><author>Wang, D.</author><author>Wang, X.</author><author>Feng, X.</author><author>Xia, M.</author></authors></contributors><auth-address>Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, China.</auth-address><titles><title>Involvement of oxygen-regulated protein 150 in AMP-activated protein kinase-mediated alleviation of lipid-induced endoplasmic reticulum stress</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>11119-31</pages><volume>286</volume><number>13</number><keywords><keyword>AMP-Activated Protein Kinases/genetics/metabolism</keyword><keyword>Aminoimidazole Carboxamide/analogs &amp; derivatives/pharmacology</keyword><keyword>Animals</keyword><keyword>Apoptosis/drug effects/genetics</keyword><keyword>Endoplasmic Reticulum/genetics/*metabolism</keyword><keyword>Forkhead Box Protein O1</keyword><keyword>Forkhead Transcription Factors/genetics/metabolism</keyword><keyword>Gene Expression Regulation/drug effects/genetics</keyword><keyword>HSP70 Heat-Shock Proteins</keyword><keyword>Hep G2 Cells</keyword><keyword>Hepatocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Hypercholesterolemia/genetics/metabolism</keyword><keyword>Hypoglycemic Agents/pharmacology</keyword><keyword>Lipid Metabolism/*physiology</keyword><keyword>Liver Diseases/genetics/metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Proteins/genetics/*metabolism</keyword><keyword>Ribonucleotides/pharmacology</keyword><keyword>Sirtuin 1/genetics/metabolism</keyword><keyword>Unfolded Protein Response/drug effects/*physiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 1</date></pub-dates></dates><isbn>1083-351X (Electronic)&#xD;0021-9258 (Linking)</isbn><accession-num>21296878</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21296878</url></related-urls></urls><custom2>3064166</custom2><electronic-resource-num>10.1074/jbc.M110.203323</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 339-341, thereby reducing the risk of developing obesity and T2D. Several phosphatases also contribute to ER stress-mediated insulin resistance. PTP1B is tethered to the ER membrane in mammalian cells and acts as a negative regulator of the insulin pathway by hydrolysing the tyrosine-phosphorylated insulin receptor and IRS-1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 342. Panzhinskiy et al. demonstrated that animals fed with HFD showed elevated levels of PTP1B protein along with the UPR markers in skeletal muscle, while, tunicamycin-induced phosphorylation of eIF2? and JNK2 was significantly attenuated in PTP1B-deficient mice. Treatment with TUDCA or silencing PTP1B reversed the reduction in myotube glucose uptake caused by tunicamycin 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 342. Similarly, skeletal muscle kidney-enriched inositol polyphosphate phosphatase (SKIP), a PIP3 (phosphatidylinositol-3,4,5-trisphosphate) phosphatase, is associated with ER stress-induced IR in skeletal muscle. SKIP heterozygous knockout mice exhibit improved systemic insulin sensitivity and are resistant to diet-induced insulin resistance 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 343. SKIP form a complex with GRP78 under resting conditions 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 344 which upon insulin stimulation relocates from the ER to the plasma membrane where it binds to the activated form of p21- activated kinase 1 (PAK1) and forms a complex with Akt2 ADDIN EN.CITE <EndNote><Cite><Author>Ijuin</Author><Year>2012</Year><RecNum>667</RecNum><DisplayText>345</DisplayText><record><rec-number>667</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>667</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ijuin, T.</author><author>Takenawa, T.</author></authors></contributors><auth-address>The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan.</auth-address><titles><title>Regulation of insulin signaling by the phosphatidylinositol 3,4,5-triphosphate phosphatase SKIP through the scaffolding function of Pak1</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>3570-84</pages><volume>32</volume><number>17</number><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Mice</keyword><keyword>Phosphatidylinositol Phosphates/*metabolism</keyword><keyword>Phosphoric Monoester Hydrolases/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword><keyword>Rats</keyword><keyword>*Signal Transduction</keyword><keyword>p21-Activated Kinases/*metabolism</keyword><keyword>rac1 GTP-Binding Protein/metabolism</keyword></keywords><dates><year>2012</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1098-5549 (Electronic) 0270-7306 (Linking)</isbn><accession-num>22751929</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22751929</url></related-urls></urls><custom2>3422014</custom2><electronic-resource-num>10.1128/MCB.00636-12</electronic-resource-num></record></Cite></EndNote>345. A recent study by Takenawa et al shows an ER stress-dependent expression of SKIP in skeletal muscle. They observed an increased expression of SKIP upon treatment with thapsigargin or tunicamycin and palmitate and higher expression of SKIP in the skeletal muscle isolated from high-fat-diet-fed mice and db/db mice than in that from wild-type mice. Silencing of SKIP restored insulin-mediated glucose uptake in L6 myocytes treated with thapsigargin and increased the insulin-dependent phosphorylation of Akt2, without affecting the expression of IRS-1. Mechanistically, ER stress promotes ATF6 and XBP1-dependent expression of SKIP in skeletal muscle, which leads to an inactivation of insulin-induced PI3-kinase signalling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 346. The aforesaid phosphatases that mediate ER stress-induced skeletal muscle insulin resistance are negative regulators of insulin signalling and are dysregulated in obese and diabetic model animals. However, till date, there is no literature which establishes phosphatase(s) in direct regulation of Akt activity, by dephosphorylating at Ser473 residue. PHLPP, a novel ser /thr phosphatases, was reported to dephosphorylate Akt at Ser473 and thus observed to be a negative regulator of insulin signalling, whose expression was elevated in obese and T2D patients. Thus, PHLPP was proposed to pivotal molecular defect in insulin-resistance states such as obesity. However, certain questions remained unanswered like 1) what is the landscape of molecular defects induced due to deregulation of PHLPP1 activity, 2) what is the molecular mechanism regulating the elevated PHLPP1 expression in insulin resistance condition and 3) ER stress has emerged as a prime cellular driver in hampering insulin signalling. Thus it will be interesting to study the correlation between PHLPP1 and ER stress response in skeletal muscle induced IR. The literature below provides broad information about the protein PHLPP and its substrates along with the molecular player associated with its activity as well as expression.1.7PHLPP: Emerging target for therapeutics Flipping a decade since discovery, PHLPP (PH domain Leucine-rich repeat Protein Phosphatase) has emerged as a key player in the pathogenesis of many human diseases, most notably cancer. PHLPP was identified by Alexandra Newton, in a quest to identify a phosphatase aptly positioned at the cell membrane to dephosphorylate Akt, through computational analysis of publicly available databases for a protein comprising of membrane targeting modules like the PH (Pleckstrin homology) domain and phosphatase domain 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58. PHLPP family comprises of three isozymes encoded by two genes: PHLPP1 expressed as two alternatively spliced variants, PHLPP1? and PHLPP1? are located on chromosome 18q21.33 and another gene PHLPP2 is present on chromosome 16q22.3 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 347. However, all the isozymes share more or less similar domain architecture but show a different affinity towards the substrate(s) (Figure 1.–).1.7.1Domain composition and function:PHLPP proteins consist of the following domains: Ras-associated domain (RA domain), PH domain (Pleckstrin homology domain), LRR domain (leucine-rich repeat), a PP2C like a phosphatase domain and PDZ ligand domain. All the three isozymes share similar domain architecture (Figure 1), which is evolutionarily conserved from yeast to humans. The yeast homolog of PHLPP, Cyr1 contains a putative Ras association (RA) domain, leucine-rich repeat (LRR) segment, as well the PP2C domain but lacks the PH domain and PDZ ligand. Interestingly, Cry1 is fused with adenyl cyclase in its C-terminal. Analyzing the evolutionary development of PHLPP along the phylogenetic alignment, C-terminal PDZ ligand was noticed to be first evolved in animals having bilateral symmetry, while the PH domain was acquired later in evolution. The PHLPP1 and PHLPP2 genes diversified post-evolution from Euteleostomi clade, however still shares a healthy homology of 58% and 63% in amino acid identity for the PP2C-like and PH domain, respectively 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ADDIN EN.CITE.DATA 58, 347. Domain architecture of PHLPP family: Unlike to its other family members of PP2C phosphatase family, PHLPP harbours the catalytic domain as well as the regulatory/scaffold domain in the same polypeptide, a feature mostly observed in tyrosine phosphatases. This unique feature of PHLPP might restrict its substrate diversity inside the cells.RA (Ras-association) domain: N-terminal of PHLPP1? and PHLPP2 isoforms harbor a globular domain of approximately 90-kDa that are predicted to interact with the Ras protein and hence termed as Ras association (RA) domain ADDIN EN.CITE <EndNote><Cite><Author>Huang</Author><Year>1997</Year><RecNum>99</RecNum><DisplayText>348</DisplayText><record><rec-number>99</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>99</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Huang, L.</author><author>Weng, X.</author><author>Hofer, F.</author><author>Martin, G. S.</author><author>Kim, S. H.</author></authors></contributors><titles><title>Three-dimensional structure of the Ras-interacting domain of RalGDS</title><secondary-title>Nat Struct Biol</secondary-title><alt-title>Nature structural biology</alt-title></titles><periodical><full-title>Nat Struct Biol</full-title><abbr-1>Nature structural biology</abbr-1></periodical><alt-periodical><full-title>Nat Struct Biol</full-title><abbr-1>Nature structural biology</abbr-1></alt-periodical><pages>609-15</pages><volume>4</volume><number>8</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Crystallography, X-Ray</keyword><keyword>DNA Mutational Analysis</keyword><keyword>GTP-Binding Proteins/*chemistry/metabolism</keyword><keyword>Models, Molecular</keyword><keyword>Molecular Sequence Data</keyword><keyword>Peptide Fragments/*chemistry/metabolism</keyword><keyword>Protein Structure, Secondary</keyword><keyword>Protein-Serine-Threonine Kinases/chemistry/metabolism</keyword><keyword>Proto-Oncogene Proteins/chemistry/metabolism</keyword><keyword>Proto-Oncogene Proteins c-raf</keyword><keyword>Proto-Oncogene Proteins p21(ras)/*chemistry/metabolism</keyword><keyword>Sequence Alignment</keyword><keyword>Ubiquitins/chemistry</keyword><keyword>ral Guanine Nucleotide Exchange Factor</keyword><keyword>rap GTP-Binding Proteins</keyword></keywords><dates><year>1997</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1072-8368 (Print) 1072-8368 (Linking)</isbn><accession-num>9253406</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/9253406</url></related-urls></urls></record></Cite></EndNote>348. However, it was reported that PHLPP1? (SCOP) associates with Ras in lipid rafts via the LRR domain (described below), which is independent of RA domain 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 349, which raise speculative questions about the functionality of RA domain in PHLPP. Also, a functionally unknown stretch of poly-Thr and poly-Ser of low-complexity is also expressed in both the isozymes. PH (Pleckstrin homology) domain: A globular structure of approximately 120 amino acids, rich in ?-strand forms the PH domain. It encodes weak membrane-targeting module with only the middle Arginine (Arg, R) of an R-x-R-x-F consensus sequence for phosphoinositide binding 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 350-352 indicating it might have a role in the protein localization on the membrane. Although its role in regulating the membrane localization of PHLPP is yet to be determined, it is observed to be essential for effective dephosphorylation of PKC-?II by PHLPPs 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 59. Further, cancer therapeutic and chemopreventive effects of ?-tocopherol, an active form of vitamin E, and its derivatives are facilitated by PH domain-dependent membrane colocalization of PHLPP and Akt leading to inactivation of Akt 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 353.LRR (leucine-rich repeat): Next to the PH domain lays a stretch of 20-21 structural motif repeats consisting of 20–30 amino acid residues enriched in Leucine (Leu) and other hydrophobic amino acid residues. These repeats display a characteristic horseshoe shape pattern due to the presence of curved parallel ?-sheet on the inner surface and ?-helices on the outer surface ADDIN EN.CITE <EndNote><Cite><Author>Kobe</Author><Year>2001</Year><RecNum>105</RecNum><DisplayText>354</DisplayText><record><rec-number>105</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>105</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Kobe, B.</author><author>Kajava, A. V.</author></authors></contributors><auth-address>Department of Biochemistry and Molecular Biology/Institute for Molecular Bioscience, University of Queensland, Brisbane, 4072, Queensland, Australia. [email protected]</auth-address><titles><title>The leucine-rich repeat as a protein recognition motif</title><secondary-title>Curr Opin Struct Biol</secondary-title><alt-title>Current opinion in structural biology</alt-title></titles><periodical><full-title>Curr Opin Struct Biol</full-title><abbr-1>Current opinion in structural biology</abbr-1></periodical><alt-periodical><full-title>Curr Opin Struct Biol</full-title><abbr-1>Current opinion in structural biology</abbr-1></alt-periodical><pages>725-32</pages><volume>11</volume><number>6</number><keywords><keyword>Amino Acid Motifs/*physiology</keyword><keyword>Animals</keyword><keyword>Humans</keyword><keyword>Leucine/metabolism/*physiology</keyword><keyword>Models, Molecular</keyword><keyword>Protein Binding</keyword><keyword>Protein Conformation</keyword><keyword>Proteins/*metabolism</keyword><keyword>Repetitive Sequences, Amino Acid/physiology</keyword></keywords><dates><year>2001</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0959-440X (Print) 0959-440X (Linking)</isbn><accession-num>11751054</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11751054</url></related-urls></urls></record></Cite></EndNote>354. LRR repeats play a vital role in regulating protein-protein interactions and hence it provides docking specificity for PHLPP e.g. The LRR domain binds guanine nucleotide-free form of K-Ras in membrane rafts and inhibits the MAPK pathway 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 349. Further, the LRR motifs of PHLPP are also essential for its nuclear localization in regulating EGFR transcript 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 355. PDZ ligand: PDZ stands for postsynaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) ligand. It comprises the last three amino acids on the C-terminal of the PHLPP protein. The PDZ ligand in PHLPP belongs to the type1 category of PDZ ligands, TPL for PHLPP1 and TAL for PHLPP2 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 347. These PDZ ligands mediate numerous scaffold interactions and hence may play a crucial role in PHLPP functionality. The integrity of the PDZ ligand is essential for recognition of Akt by PHLPP in cells 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58. Further, the ability of PHLPP to dephosphorylate Akt is enhanced in presence of three scaffolding proteins, FKBP51 (FK506-binding protein of 51 kDa) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 356, Scribble 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 357, and NHERF1 (Na+/H+ exchanger regulatory factor 1) 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ADDIN EN.CITE.DATA 358, that helps in co-localizing the two enzymes. The membrane proteins Scribble and NHERF1 direct PHLPP1 to the plasma membrane promoting dephosphorylation of Akt. These scaffold protein interactions are mediated directly by the PDZ ligand (e.g. interaction between PHLPP1 and PDZ domains of NHERF1).Phosphatase domain (PP2C like): PHLPP is placed under a distinct subclass within the PP2C group of the protein phosphatase metal-dependent (PPM) family of Ser/Thr phosphatases. Similar to the members of the family, PHLPP requires divalent cations like Mn2+ for its catalytic activity but uniquely remains insensitive to the known phosphatase inhibitors like okadaic acid or calyculin-A or other natural products such as microcystin LR or cyclosporine. However, two selective inhibitors of PHLPP activity are identified, NSC117079 (1-amino-9,10-dioxo-4-(3-sulfamoylanilino) anthracene-2-sulfonic acid, sodium salt) and NSC45586 (1,3-4-(2,4-diamino-5-methyl phenyl) diazenylphenyl hydrazinylidene-6-oxocyclohexa-1,4-diene-1-carboxylic acid), which enhance Akt phosphorylation, reduce apoptosis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 359, down-regulate chaperone-mediated autophagy 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 360, stimulate chondrocyte proliferation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 361, and promote Akt dependent neuroprotective activity in rat cortical neurons 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 362. Unique active site architecture of PHLPP-PP2C domain: A typical mammalian PP2C domain has a characteristic centrally buried two anti-parallel ?-sheets flanked by two anti-parallel ?-helices, with a catalytic core made of two Mn2+ ions coordinated by four conserved Aspartate (Asp) residues and a variable Glutamate (Glu). Newton’s group using point mutation analyses deciphered the unusual active site architecture of PHLPP2 upon comparison with canonical PP2C alpha sites. They identified three acidic residues (canonical PP2C has four acidic residues) which are likely to form the coordinates for the metal ion; Asp806, Glu 989 and Asp1024 in PHLPP2 (corresponding to Asp60, Asp239 and Asp282 in PP2C?, Asp698 and Asp879 and Asp901 in PHLPP1), mutation of which significantly impaired activity of PHLPP2. Further, a mutation of a unique bulk Phe808 residue (present at the end of the ?4 sheet), found only in PHLPP2, nearly deactivated the enzyme, as it is assumed to form an essential ?-stacking interaction with Phe783 (present at the beginning of ?3 sheet) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 363. Thus, PHLPP2 exhibits a unique active site microenvironment with considerable differences in the key amino acid residues in comparison to the known PP2C phosphatases. However, the currently active site architecture was based on isolated PP2C like domain, the impact of other scaffolding domains including LRR and PH on the folding of the PP2C domain need to be assessed for its effect on the activity of the phosphatase. Biochemical characterization of the catalytic activity:With overall 68% homology in the PP2C domain, both PHLPP1 and PHLPP2 exhibited an identical kinetic profile under defined conditions. Both the isozymes showed a similar affinity towards pNPP (p-nitrophenyl phosphate) (KM = 2.1 ± 0.2 mM for PHLPP1 and 1.80 ± 0.08 mM for PHLPP2) and substrate-specific synthetic phosphopeptides like serine-phosphorylated peptide sequence of the hydrophobic motif of Akt (HFPQFpSYSAS), irrespective of the enzyme source. However, a higher catalytic activity towards pNPP was noticed with insect purified enzyme compared to bacterial origin protein, but both showed similar catalytic activity for synthetic phosphopeptides (Akt- HFPQFpSYSAS, a sequence conversed across the isoforms, Akt1-3) or threonine-phosphorylated peptide (RRAPTVA), a standard substrate for PP2C) (reference), indicating protein folding might play a role in defining substrate affinity. Unlike to the other PP2C family members, PHLPP dependence on metal ions for its activity is more complex than the other PP2C members. Enzymatic activity was noted even in the absence of divalent cation in the reaction. In fact, the addition of chelating agents such as EDTA at concentrations as high as 100mM didn’t show any effect on dephosphorylation of the pPNPP substrate by PHLPP2-PP2C. Interestingly adding bivalent cations ions like Ca+2, Cu+2, Zn+2, and Ni+2 inhibited the phosphatase activity. While the addition of Mg+2 doesn’t affect the phosphatase kinetics, the influence of Mn+2 was more complex. Adding Mn+2 to the reaction containing mammalian cell purified protein (PP2C) enhanced the rate of reaction (dephosphorylation). Conversely, Mn+2, when added to the dephosphorylation reaction with protein purified from a bacterial source, inhibited the reaction. The author predicted that conflicting result may be due to alteration of pH in the reaction mixture, however further in-depth analysis is required to completely define the dependency of PHLPP on the metal ion, especially Mn+2. Moreover, analyzing the influence of other parameters like oxidizing agents (DTT) and fatty acids has given a broader spectrum in understanding the phosphatase activity. Addition of DTT (0.4-8mM) significantly enhanced the PHLPP1 activity (max activity at <3mM DTT). However, the addition of DTT in the reaction had minimal impact on PHLPP2-PP2C activity. On the other hand addition of fatty acids, either in presence of or absence of Mn+2 ion enhanced the PP2C dephosphorylation activity 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ADDIN EN.CITE.DATA 363. 17.2Substrates of PHLPP:Considering the abundance of sites phosphorylated at Ser/Thr residues in cells and the limited number of known Ser/Thr phosphatases, it is not surprising that PHLPP1/2 might have numerous targets. Identified as a phosphatase that can directly dephosphorylate Akt, PHLPP1/2 has completed its thirteen years since discovered with five bonafide substrates. PHLPP as the hydrophobic motif phosphatase: PHLPP dephosphorylates some of the AGC kinases in their hydrophobic pocket and suppresses their activity. AGC kinases for their maximal activation require phosphorylation at two conserved segments: 1) the activation loop: Phosphorylation at this segment aligns the residues in the correct orientation for catalysis, and 2) C-terminal segment: This segment comprises of two phosphorylation sites the “turn-motif” and the “hydrophobic motif.” Phosphorylation at both the sites is essential for the complete activation of the kinases ADDIN EN.CITE <EndNote><Cite><Author>Pearce</Author><Year>2010</Year><RecNum>182</RecNum><DisplayText>364</DisplayText><record><rec-number>182</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>182</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Pearce, L. R.</author><author>Komander, D.</author><author>Alessi, D. R.</author></authors></contributors><auth-address>MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. [email protected]</auth-address><titles><title>The nuts and bolts of AGC protein kinases</title><secondary-title>Nat Rev Mol Cell Biol</secondary-title><alt-title>Nature reviews. Molecular cell biology</alt-title></titles><periodical><full-title>Nat Rev Mol Cell Biol</full-title><abbr-1>Nature reviews. Molecular cell biology</abbr-1></periodical><alt-periodical><full-title>Nat Rev Mol Cell Biol</full-title><abbr-1>Nature reviews. Molecular cell biology</abbr-1></alt-periodical><pages>9-22</pages><volume>11</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus/enzymology</keyword><keyword>Enzyme Activation</keyword><keyword>Humans</keyword><keyword>Neoplasms/enzymology</keyword><keyword>Protein-Serine-Threonine Kinases/*chemistry/*physiology</keyword></keywords><dates><year>2010</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1471-0080 (Electronic) 1471-0072 (Linking)</isbn><accession-num>20027184</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20027184</url></related-urls></urls><electronic-resource-num>10.1038/nrm2822</electronic-resource-num></record></Cite></EndNote>364. PHLPP was identified as a phosphatase that can directly dephosphorylate Akt at the membrane on a key regulatory residue of Ser473 located at the C-terminal hydrophobic pocket, decreasing its intrinsic catalytic activity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58. Interestingly, the PHLPP isoforms show specificity in their regulation of different Akt isoforms. PHLPP1 inactivates Akt2 and Akt3, but not Akt1, whereas PHLPP2 dephosphorylates Akt1 and Akt3, but not Akt2 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 347. This specificity towards different Akt isoforms helps it to achieve differential regulation of various AKT substrates 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 365. Later, other AGC kinases like protein kinase C (PKC) ?II and ribosomal protein S6 kinase were identified to be directly dephosphorylated by PHLPP1/2. PKC?II is dephosphorylated at Ser660 resulting in reduced steady-state levels of the enzyme 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 59 and ribosomal protein S6 kinase at Thr389 reducing its activity resulting in decreased protein translation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 366. This selectivity dephosphorylation of PHLPP in the hydrophobic motif of the substrates might be due to the presence of some signature residues like Phe at the P-1 position in the hydrophobic pocket of the substrate that results in unique interactions between the motif and substrate binding cavity of the phosphatase domain 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 359. In addition, non-AGC kinases like the pro-apoptotic kinase mammalian sterile 20-like kinase 1 (Mst1), a member of the STE kinase family, is also a bonafide substrate of PHLPP 18. PHLPP activates Mst1 by dephosphorylating an inhibitory phosphorylation on Mst1 at Thr387, which in turn leads to activation of p38 and JNK to induce apoptosis and growth arrest. PHLPP further potentiates the activation of Mst1 by inactivating Akt which phosphorylates the inhibitory activation site (Thr387) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 367. Thereby, PHLPP inactivates pro-survival pathways and promotes pro-apoptotic signalling, supporting its tumour suppressor role.PHLPP as an inhibitor of MAPK signalling: Prior to the discovery of PHLPP, Shimizu et al. identified a gene called SCOP (which is PHLPP1?), who’s mRNA levels oscillate in a circadian manner, suggesting of a role in controlling the central clock 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 368. In neuronal cell systems, SCOP through its LRR region was observed to bind the nucleotide-free form of K-Ras, thereby preventing GTP binding and thus restricting of MEK/ERK pathway 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 349. Hence upon ectopic expression of PHLPP1 in the hippocampi of mice reduces ERK1/2 signalling, which in turn inhibited cAMP response element-mediated transcription, resulting in impair long-term memory formation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 369. While, PHLPP1 knockout mice exhibited a delayed shortening of circadian period length (tau) and impaired capacity to stabilize the circadian rhythm, in response to a light-induced phase shift ADDIN EN.CITE <EndNote><Cite><Author>Shimizu</Author><Year>2010</Year><RecNum>2</RecNum><DisplayText>370</DisplayText><record><rec-number>2</rec-number><foreign-keys><key app=”EN” db-id=”axttxaxdmef22lee5tt5rxt5rd09xf02z0tr”>2</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Shimizu, K.</author><author>Mackenzie, S. M.</author><author>Storm, D. R.</author></authors></contributors><auth-address>Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.</auth-address><titles><title>SCOP/PHLPP and its functional role in the brain</title><secondary-title>Mol Biosyst</secondary-title></titles><pages>38-43</pages><volume>6</volume><number>1</number><edition>2009/12/22</edition><keywords><keyword>Animals</keyword><keyword>Brain/*metabolism/physiology</keyword><keyword>Circadian Rhythm/physiology</keyword><keyword>Humans</keyword><keyword>Memory/physiology</keyword><keyword>Mice</keyword><keyword>Mitogen-Activated Protein Kinase 1/metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 3/metabolism</keyword><keyword>Models, Biological</keyword><keyword>Nuclear Proteins/chemistry/genetics/metabolism/*physiology</keyword><keyword>Phosphoprotein Phosphatases/chemistry/genetics/metabolism/physiology</keyword><keyword>Rats</keyword></keywords><dates><year>2010</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1742-2051 (Electronic) 1742-2051 (Linking)</isbn><accession-num>20024065</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20024065</url></related-urls></urls><custom2>3487473</custom2><electronic-resource-num>10.1039/b911410f</electronic-resource-num><language>eng</language></record></Cite></EndNote>370. Thus, taking together the above observation PHLPP1 is considered to play a vital role in maintaining neural plasticity and in resetting the circadian clock in response to changing stimuli. Similarly to the above observations, we also observed a stimulus-specific inhibition of Erk1/2 phosphorylation by PHLPP1 in macrophages. IFN? induced Erk1/2 phosphorylation in mouse macrophages was observed to be sensitive to PHLPP1 levels whereas LPS induced Erk1/2 phosphorylation was unaltered ADDIN EN.CITE <EndNote><Cite><Author>Alamuru</Author><Year>2014</Year><RecNum>71</RecNum><DisplayText>371</DisplayText><record><rec-number>71</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>71</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Alamuru, N. P.</author><author>Behera, S.</author><author>Butchar, J. P.</author><author>Tridandapani, S.</author><author>Kaimal Suraj, S.</author><author>Babu, P. P.</author><author>Hasnain, S. E.</author><author>Ehtesham, N. Z.</author><author>Parsa, K. V.</author></authors></contributors><auth-address>Dr. Reddy's Institute of Life Sciences (DRILS), Hyderabad, India. Department of Biotechnology, University of Hyderabad, Hyderabad, India. Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA. Department of Biological Sciences, Indian Institute of Technology, New Delhi, India; and. National Institute of Pathology, Safdarjung Hospital, New Delhi, India. Dr. Reddy's Institute of Life Sciences (DRILS), Hyderabad, India; [email protected].</auth-address><titles><title>A novel immunomodulatory function of PHLPP1: inhibition of iNOS via attenuation of STAT1 ser727 phosphorylation in mouse macrophages</title><secondary-title>J Leukoc Biol</secondary-title><alt-title>Journal of leukocyte biology</alt-title></titles><periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></periodical><alt-periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></alt-periodical><pages>775-783</pages><volume>95</volume><number>5</number><dates><year>2014</year><pub-dates><date>May</date></pub-dates></dates><isbn>1938-3673 (Electronic) 0741-5400 (Linking)</isbn><accession-num>24443556</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24443556</url></related-urls></urls><electronic-resource-num>10.1189/jlb.0713360</electronic-resource-num></record></Cite></EndNote>371. In addition to the above indirect inhibition, PHLPP1/2 has been recently reported to directly constrain MAPK pathway dephosphorylating RAF1. Abnormalities in MAPK signalling are associated with development and progression of several cancers, with Ras–Raf axis as the regulatory hotspot of the pathway. Rare incidence of mutation in both Ras and Raf in the same tumour cell makes Raf be one of the main effector pathways of MAPK in human carcinogenesis. Recently, RAF1 has been identified as a direct substrate of PHLPP1/2 in colorectal cancer (CRC) cells. PHLPP1/2 directly dephosphorylation of RAF1 at Ser338 site thereby inactivating MAPK signalling both in vitro and in CRC cells 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ADDIN EN.CITE.DATA 372. Ablation of PHLPP1/2 in CRC cells induced epithelial-mesenchymal transition (EMT) with increased migration and invasion in vitro. Similarly, knockout of PHLPP1 in ApcMin mice (ApcMin/Phlpp1?/? mice) resulted in invasive adenocarcinomas and decreased survival compared to the ApcMin mice. These above findings implicate a complex role for PHLPP in restricting MAPK signalling. PHLPP as a novel regulator of histone and chromosome integrity:Histones are the essential components of eukaryotic genome architecture. Eukaryotic genomic DNA condenses around the histone protein forming the nucleosomes, the functional units of chromatin ADDIN EN.CITE <EndNote><Cite><Author>Kornberg</Author><Year>1974</Year><RecNum>183</RecNum><DisplayText>373</DisplayText><record><rec-number>183</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>183</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Kornberg, R. D.</author></authors></contributors><titles><title>Chromatin structure: a repeating unit of histones and DNA</title><secondary-title>Science</secondary-title><alt-title>Science</alt-title></titles><periodical><full-title>Science</full-title><abbr-1>Science</abbr-1></periodical><alt-periodical><full-title>Science</full-title><abbr-1>Science</abbr-1></alt-periodical><pages>868-71</pages><volume>184</volume><number>4139</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Cattle</keyword><keyword>Chromatin/*analysis/metabolism</keyword><keyword>*DNA/metabolism</keyword><keyword>Drosophila</keyword><keyword>Endonucleases/metabolism</keyword><keyword>*Histones</keyword><keyword>Molecular Weight</keyword><keyword>Nucleic Acid Conformation</keyword><keyword>Protein Conformation</keyword><keyword>Thymus Gland/analysis</keyword><keyword>X-Ray Diffraction</keyword></keywords><dates><year>1974</year><pub-dates><date>May 24</date></pub-dates></dates><isbn>0036-8075 (Print) 0036-8075 (Linking)</isbn><accession-num>4825889</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/4825889</url></related-urls></urls></record></Cite></EndNote>373. Chemical modifications of histone tail via phosphorylation or acetylation can alter chromatin structure influencing gene expression, DNA replication, and DNA repair ADDIN EN.CITE <EndNote><Cite><Author>Sawan</Author><Year>2010</Year><RecNum>117</RecNum><DisplayText>374</DisplayText><record><rec-number>117</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>117</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Sawan, C.</author><author>Herceg, Z.</author></authors></contributors><auth-address>Epigenetics Group, International Agency for Research on Cancer ,69008 Lyon, France.</auth-address><titles><title>Histone modifications and cancer</title><secondary-title>Adv Genet</secondary-title><alt-title>Advances in genetics</alt-title></titles><periodical><full-title>Adv Genet</full-title><abbr-1>Advances in genetics</abbr-1></periodical><alt-periodical><full-title>Adv Genet</full-title><abbr-1>Advances in genetics</abbr-1></alt-periodical><pages>57-85</pages><volume>70</volume><keywords><keyword>Cell Transformation, Neoplastic</keyword><keyword>Chromatin/*genetics/*metabolism</keyword><keyword>DNA Repair/genetics</keyword><keyword>DNA Replication/genetics</keyword><keyword>*Epigenesis, Genetic</keyword><keyword>Histone Code</keyword><keyword>Histones/*genetics/*metabolism</keyword><keyword>Humans</keyword><keyword>Mitosis/genetics</keyword><keyword>Neoplasms/diagnosis/*genetics/*metabolism/therapy</keyword><keyword>Transcription, Genetic</keyword><keyword>Transcriptional Activation/genetics</keyword></keywords><dates><year>2010</year></dates><isbn>0065-2660 (Print) 0065-2660 (Linking)</isbn><accession-num>20920745</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20920745</url></related-urls></urls><electronic-resource-num>10.1016/B978-0-12-380866-0.60003-4</electronic-resource-num></record></Cite></EndNote>374. Loss of PHLPP1 is associated with enhanced phosphorylation and acetylation of histone 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 355, a condition observed in actively transcribing genome. For instance increased promoter acetylation of the epidermal growth factor receptor (EGFR), resulting in increased transcription and increased steady-state levels of the EGFR is reported upon loss of PHLPP 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 355. Similarly increased steady-state levels of other receptor tyrosine kinases (RTKs), such as the platelet-derived growth factor receptor and the insulin receptor, are also observed upon depletion of PHLPP1 protein. The epigenetic role of PHLPP is likely to play a major tumour suppressor role in diverse human cancers associated with amplified signalling by RTKs ADDIN EN.CITE <EndNote><Cite><Author>Hynes</Author><Year>2005</Year><RecNum>185</RecNum><DisplayText>375</DisplayText><record><rec-number>185</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>185</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Hynes, N. E.</author><author>Lane, H. A.</author></authors></contributors><auth-address>Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. [email protected]</auth-address><titles><title>ERBB receptors and cancer: the complexity of targeted inhibitors</title><secondary-title>Nat Rev Cancer</secondary-title><alt-title>Nature reviews. Cancer</alt-title></titles><periodical><full-title>Nat Rev Cancer</full-title><abbr-1>Nature reviews. Cancer</abbr-1></periodical><alt-periodical><full-title>Nat Rev Cancer</full-title><abbr-1>Nature reviews. Cancer</abbr-1></alt-periodical><pages>341-54</pages><volume>5</volume><number>5</number><keywords><keyword>Animals</keyword><keyword>Antibodies, Monoclonal/*therapeutic use</keyword><keyword>Antineoplastic Agents/*therapeutic use</keyword><keyword>Antineoplastic Combined Chemotherapy Protocols/therapeutic use</keyword><keyword>Drug Delivery Systems</keyword><keyword>Drug Resistance, Neoplasm</keyword><keyword>Humans</keyword><keyword>Neoplasms/*drug therapy/*etiology</keyword><keyword>Receptor Protein-Tyrosine Kinases/antagonists & inhibitors</keyword><keyword>Receptor, ErbB-2/antagonists & inhibitors/immunology/*physiology</keyword><keyword>Signal Transduction/drug effects</keyword></keywords><dates><year>2005</year><pub-dates><date>May</date></pub-dates></dates><isbn>1474-175X (Print) 1474-175X (Linking)</isbn><accession-num>15864276</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15864276</url></related-urls></urls><electronic-resource-num>10.1038/nrc1609</electronic-resource-num></record></Cite></EndNote>375. In addition to above, PHLPP1 also plays an important role in proper segregation of sister chromatids during mitosis. Precise attachment of sister chromatids to opposite spindle poles, during mitosis, is governed by a group of specialized proteins called kinetochores. Kinetochores are assembled on centromeric DNA that connects to spindle microtubules 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ADDIN EN.CITE.DATA 376, 377 and is comprised of three distinct protein layers, an inner core kinetochore, an outer kinetochore, and a fibrous corona 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 378. PHLPP1 is reported to dephosphorylated SGT1 (suppressor of G2 allele of SKP1 homolog), an essential outer kinetochore protein 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 379, 380, at four conserved residues (Ser-17, Ser-249, Ser-289, and Thr-233) which prevents it association with ring finger protein 41 (RNF41) an E3 ligase, thereby maintaining an optimal SGT1 protein levels during early mitosis which facilitates proper kinetochore assembly 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 381.1.7.3Multifaceted Regulation of PHLPP:Given the critical role of PHLPP in controlling multiple cellular processes, regulation of PHLPP expression has gained a lot of importance in the last few years. Below we discuss mechanisms reported to regulate PHLPP functionality. Epigenetic modulations: Epigenetics is the study of genes regulation in somatic as well as germ cells that is independent of its genetic code. Epigenetic regulation is mainly achieved by DNA methylation, histone modifications, chromatin remodeling, microRNAs and other noncoding regulatory RNAs. Epigenetic modulations like DNA hypermethylation and/or histone deacetylation of tumor suppressor genes, resulting in downregulation and/or silencing, are frequently observed in numerous cancers 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 382, 383. DNA methylation is a stable covalent modification and was the first non-genetic event to be directly associated with human cancer more than three decades ago (reference). Deregulation of tumor DNA, such as promoter-specific hypermethylation and global hypomethylation has been observed in most of the pathological conditions (reference). Similarly assessing the methylation status of PHLPP1 in CLL cells, O’Hayre et al. noted that the end of the exon1 coding region of PHLPP1 was hypermethylated which correlated with loss of PHLPP1 expression in chronic lymphocytic leukemia (CLL) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 384. On the other hand, Bradley and colleagues, while exploring the role of PHLPP in osteoarthritis (OA) observed hypomethylation of the PHLPP1 promoter in human patient samples which positively associated with augmentation of PHLPP1 expression in cartilage tissues. Consistently, PHLPP1-/- mice were noted to be less prone to cartilage deterioration and showed fewer signs of OA, following DMM (expand) surgeries 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 385, indicating that PHLPP expression is tightly regulated by DNA methylation in multiple tissues. Epigenetic plasticity in regulating the gene expression is also achieved by post-translation modification of histones such as acetylation/deacetylation and phosphorylation/ dephosphorylation. Apart from analyzing the promoter methylation of PHLPP, Bradley et al also studied the histone acetylation pattern of PHLPP promoter. They observed that HDAC3 was constitutively bound to PHLPP promoter region containing SMAD binding elements. Importantly, TGF? exposure activated SMAD mediated signalling which resulted in the release of HDAC3 from PHLPP promoter and subsequently enhanced the expression of PHLPP1 but not PHLPP2. Furthermore, HDAC3 inhibitors like suberoylanilide hydroxamic acid (SAHA, Vorinostat), or trichostatin A (TSA) also enhanced PHLPP1 expression, which firmly established HDAC3 epigenetic regulation by modifying chromatin and influencing PHLPP gene expression in osteoblasts 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 386.Transcriptional alterations: The recent developments in the understanding of cellular gene expression patterns had been a vital tool in enhancing our understanding of the progression of numerous pathological conditions. Many different diseases and syndromes, including cancer, diabetes, neurological disorders, cardiovascular disease, autoimmunity, and obesity, are noticed to be deregulated by hyperactivity of transcription factors, cofactors, chromatin regulators as well as noncoding RNAs that interact within these specific regions. Although PHLPP has emerged as an important player in the specific and dynamic regulation of cellular processes, its transcriptional regulation has remained underexplored.Preliminary studies of transcriptional regulation of PHLPP were pursued by Patterson et al. While addressing the critical question of minimal PI3K activity during the development of Tregs cells, the authors noticed transcriptional upregulation of PHLPP1 (and PHLPP2) in Treg cells compared to the Tconv cells. Mechanistic analysis indicated that TGF? induced SMAD transcription factors recruitment to the PHLPP promoter was enhanced which was directly correlated with increased transcription of PHLPP 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ADDIN EN.CITE.DATA 387. Conversely, Saavedra et al, while exploring the function of PHLPP in Huntington disease (HD) noted a significant decrease of PHLPP expression in cultured cells, mice, and human patients’ samples. They proposed that observed depletion of PHLPP expression may be due to sequestration of NF-Y transcription factor which was 1) established to repress HSP90 expression in HD disease, 2) Matrix search for the potential PHLPP promoter binding sites identified NF-Y as a potential regulator PHLPP expression. However, cellular and functional validations are still not established to define NF-Y dependent PHLPP expression 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 388. Recently we reported that bacterial endotoxin LPS depletes PHLPP1 transcript in a time-dependent manner. Exploring the molecular machinery associated with PHLPP1 transcriptional regulation in macrophages, we identified that PHLPP1 is tightly controlled by SP1 activity. SP1 with the assistance of histone acetyltransferase co-activators CBP/Ep300 enhanced the transcriptional activity of the PHLPP1 promoter in macrophages 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 389. Further, the expression of SP1 along with CBP was noted to be reduced in a time-dependent manner upon LPS treatment. Importantly, the recruitment of SP1 to PHLPP1 promoter was also noticed to be attenuated in LPS stimulated macrophages 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 389.Recently, another transcriptional regulation of PHLPP1 by c-JUN was reported in nickel-induced lung tumorigenesis. C-JUN was observed to be constitutively bound to PHLPP1 promoter thereby suppressing its transcription. Epigenetic repression of maternally expressed gene 3 (MEG3), a long noncoding RNAs (lncRNAs), diminishes its association with c-JUN which resulted in transcription repression of PHLPP1 by c-JUN and upregulation of HIF-1? via activation of Akt/p70S6K/S6 axis, to promote malignant transformation of human bronchial epithelial cells 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ADDIN EN.CITE.DATA 390. Considering a strong association between PHLPP transcript levels and numerous clinical observations, assessing the promoter activity of PHLPP in depth will be of significance.Post-transcriptional regulation:MicroRNAs or miRNAs are a subset of non-coding RNAs ~22-nt long endogenously synthesized short RNA molecules that are considered to post-transcriptionally regulate the cleavage of target mRNAs or just repress their translation. Alteration of miRNA expression profiling has been associated with multiple clinical observations and is investigated as possible biomarkers for diagnosis, prognosis, and prediction of several diseases. miRNA based studies have recently been exploited with the major focus on developing novel therapies either alone or in conjugation with current targeted therapies. Hence, deciphering the potential miRNA based regulation of vital protein like PHLPP has gained importance in the last couple of years. Jiang et al. while addressing the molecular mechanism of oncomiR-17-92 mediated tumor development proposed that the polycistronic miR-17-92, which encodes for seven different miRNAs, might regulate the expression of PHLPP2 and PTEN in promoting radio-resistance in human mantle cell lymphoma ADDIN EN.CITE <EndNote><Cite><Author>Jiang</Author><Year>2010</Year><RecNum>131</RecNum><DisplayText>391</DisplayText><record><rec-number>131</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>131</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Jiang, P.</author><author>Rao, E. Y.</author><author>Meng, N.</author><author>Zhao, Y.</author><author>Wang, J. J.</author></authors></contributors><auth-address>Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China.</auth-address><titles><title>MicroRNA-17-92 significantly enhances radioresistance in human mantle cell lymphoma cells</title><secondary-title>Radiat Oncol</secondary-title><alt-title>Radiation oncology</alt-title></titles><periodical><full-title>Radiat Oncol</full-title><abbr-1>Radiation oncology</abbr-1></periodical><alt-periodical><full-title>Radiat Oncol</full-title><abbr-1>Radiation oncology</abbr-1></alt-periodical><pages>100</pages><volume>5</volume><keywords><keyword>Apoptosis/genetics/radiation effects</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Proliferation/radiation effects</keyword><keyword>Cell Separation</keyword><keyword>Flow Cytometry</keyword><keyword>Gene Expression/radiation effects</keyword><keyword>Humans</keyword><keyword>Immunoblotting</keyword><keyword>Lymphoma, Mantle-Cell/*genetics/*radiotherapy</keyword><keyword>MicroRNAs/*genetics</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Radiation Tolerance/*genetics</keyword><keyword>Transfection</keyword></keywords><dates><year>2010</year><pub-dates><date>Nov 01</date></pub-dates></dates><isbn>1748-717X (Electronic) 1748-717X (Linking)</isbn><accession-num>21040528</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21040528</url></related-urls></urls><custom2>2984457</custom2><electronic-resource-num>10.1186/1748-717X-5-100</electronic-resource-num></record></Cite></EndNote>391. The study was further confirmed by Kelekae and group while assessing the C/EBP-? induced PHLPP2 expression in acute myeloid leukemia (AML) cells 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 392. They reported that C/EBP-?, an all-trans-retinoic acid (ATRA) responsive transcription factor, mediates the repression of the oncomir cluster by directly interacting with the intronic promoter of miR-17-92 gene. As a result, the expression of miRs was diminished, subsequently, PHLPP2 protein expression was enhanced. However, the first detailed study in miRNA based regulation of PHLPP was reported by Beezhold et al. decoding the underlying mechanism of arsenic-induced malignant transformation, the authors noticed that dose-dependent arsenic-induced expression of miR-190 which attenuated the translation of PHLPP by targeting its 3′ UTR. Due to the reduction of PHLPP expression upon arsenic exposure, Akt activity was noticed to be upregulated which resulted in the malignant transformation of normal cells 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 393. In another two independent reports, PHLPP was observed to be regulated by miR-331-3p and miR-3127 in hepatocellular carcinoma (HCC). miR-331-3p was shown to target PHLPP1 mRNA transcript, but not PHLPP2 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 394, while miR-3127 was found to regulate both PHLPP1 and PHLPP2 mRNA expression 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 395. Based on the data from multiple cell-based studies, xenograft, animal models and clinical datasets, authors concluded that miR-331-3p and miR-3127 deplete PHLPP expression which was directly associated with proliferation, migration, and metastasis of HCC. Recently Cui et al. established that miR-3117 targets PHLPPL (an isoform of PHLPP1) in promoting hepatocellular carcinoma cell proliferation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 396. Similar to miR17-92, miR-205 was also reported to target the 3′-UTR of PHLPP2 and PTEN in non-small cell lung cancer (NSCLC) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 397. Consistent with the literature, upregulation of miR-205 depleted PTEN and PHLPP2 expression leading to sustained phosphorylation of Akt promoting growth, neovascularization, and development of NSCLC. In another independent study, miR-141 was reported to downregulate the expression of both PHLPP1 and PHLPP2 resulting in enhanced AKT activity that accelerated NSCLC cell proliferation in vitro and tumor growth in vivo. Importantly, the reintroduction of PHLPP1 and PHLPP2 abrogated the proliferative effect of miR-141 on NSCLC cells 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 398. Consistent with the above literature, miR-522, miR-372 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 399 and miR-93 were noted to regulate PHLPP expression in human glioblastoma cells, in two independent studies. Zhang et al while studying the role of miR-522 in glioblastoma, established PHLPP1 as the putative target of the microRNA, which was proposed to be the main contributor to the tumor growth 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ADDIN EN.CITE.DATA 400. Similarly, Jiang and colleagues noted that miR-93 was upregulated in glioma which promotes cellular proliferation and cell cycle progression. Addressing the molecular insights, authors noted that miR-93 suppresses the expression of PHLPP2, PTEN, and Foxo3 by targeting the 3′ UTR of the respective genes 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Similarly, miR-27a, miR-493, miR-135a, miR-938 and miR-760 promote gastric, prostate, bladder, colorectal cancer and ovarian cancer cell proliferation by suppressing PHLPP2 expression and thus promoting tumorigenesis <EndNote><Cite><Author>Ding</Author><Year>2017</Year><RecNum>139</RecNum><DisplayText>[402-406]</DisplayText><record><rec-number>139</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">139</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ding, L.</author><author>Zhang, S.</author><author>Xu, M.</author><author>Zhang, R.</author><author>Sui, P.</author><author>Yang, Q.</author></authors></contributors><auth-address>Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin Province, China.&#xD;Department of Orthopedics, The Second Hospital, Jilin University, Changchun, Jilin, China.&#xD;Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin Province, China. yangq@jlu.edu.cn.</auth-address><titles><title>MicroRNA-27a contributes to the malignant behavior of gastric cancer cells by directly targeting PH domain and leucine-rich repeat protein phosphatase 2</title><secondary-title>J Exp Clin Cancer Res</secondary-title><alt-title>Journal of experimental &amp; clinical cancer research : CR</alt-title></titles><periodical><full-title>J Exp Clin Cancer Res</full-title><abbr-1>Journal of experimental &amp; clinical cancer research : CR</abbr-1></periodical><alt-periodical><full-title>J Exp Clin Cancer Res</full-title><abbr-1>Journal of experimental &amp; clinical cancer research : CR</abbr-1></alt-periodical><pages>45</pages><volume>36</volume><number>1</number><dates><year>2017</year><pub-dates><date>Mar 21</date></pub-dates></dates><isbn>1756-9966 (Electronic)&#xD;0392-9078 (Linking)</isbn><accession-num>28327189</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28327189</url></related-urls></urls><custom2>5361803</custom2><electronic-resource-num>10.1186/s13046-017-0516-2</electronic-resource-num></record></Cite><Cite><Author>Mao</Author><Year>2015</Year><RecNum>143</RecNum><record><rec-number>143</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">143</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mao, X. P.</author><author>Zhang, L. S.</author><author>Huang, B.</author><author>Zhou, S. Y.</author><author>Liao, J.</author><author>Chen, L. W.</author><author>Qiu, S. P.</author><author>Chen, J. X.</author></authors></contributors><auth-address>Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. mxpzc1979@163.com.&#xD;Oncology Department, PLA458 Hospital, Guangzhou, 510000, China. lawysun@163.com.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. huangbin2007@yahoo.com.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. zhoushying@yeah.net.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. junliaogz@163.com.&#xD;Oncology Department, PLA458 Hospital, Guangzhou, 510000, China. lingwuch@126.com.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. qiushp@mail.sysu.edu.cn.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. chenjunxindoctor@163.com.</auth-address><titles><title>Mir-135a enhances cellular proliferation through post-transcriptionally regulating PHLPP2 and FOXO1 in human bladder cancer</title><secondary-title>J Transl Med</secondary-title><alt-title>Journal of translational medicine</alt-title></titles><periodical><full-title>J Transl Med</full-title><abbr-1>Journal of translational medicine</abbr-1></periodical><alt-periodical><full-title>J Transl Med</full-title><abbr-1>Journal of translational medicine</abbr-1></alt-periodical><pages>86</pages><volume>13</volume><keywords><keyword>Base Sequence</keyword><keyword>Cell Cycle/genetics</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Proliferation</keyword><keyword>Cyclin D1/metabolism</keyword><keyword>Cyclin-Dependent Kinase Inhibitor p21/metabolism</keyword><keyword>Cyclin-Dependent Kinase Inhibitor p27/metabolism</keyword><keyword>Forkhead Box Protein O1</keyword><keyword>Forkhead Transcription Factors/*genetics/metabolism</keyword><keyword>*Gene Expression Regulation, Neoplastic</keyword><keyword>Humans</keyword><keyword>Ki-67 Antigen/metabolism</keyword><keyword>MicroRNAs/genetics/*metabolism</keyword><keyword>Models, Biological</keyword><keyword>Molecular Sequence Data</keyword><keyword>Phosphoprotein Phosphatases/*genetics/metabolism</keyword><keyword>*Transcription, Genetic</keyword><keyword>Urinary Bladder Neoplasms/*genetics/*pathology</keyword></keywords><dates><year>2015</year><pub-dates><date>Mar 13</date></pub-dates></dates><isbn>1479-5876 (Electronic)&#xD;1479-5876 (Linking)</isbn><accession-num>25888950</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25888950</url></related-urls></urls><custom2>4367980</custom2><electronic-resource-num>10.1186/s12967-015-0438-8</electronic-resource-num></record></Cite><Cite><Author>Li</Author><Year>2017</Year><RecNum>137</RecNum><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, C. F.</author><author>Li, Y. C.</author><author>Jin, J. P.</author><author>Yan, Z. K.</author><author>Li, D. D.</author></authors></contributors><auth-address>Department of Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun 130033, China.&#xD;Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China. Electronic address: yongchaolijl@163.com.</auth-address><titles><title>miR-938 promotes colorectal cancer cell proliferation via targeting tumor suppressor PHLPP2</title><secondary-title>Eur J Pharmacol</secondary-title><alt-title>European journal of pharmacology</alt-title></titles><periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></periodical><alt-periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></alt-periodical><pages>168-173</pages><volume>807</volume><dates><year>2017</year><pub-dates><date>Jul 15</date></pub-dates></dates><isbn>1879-0712 (Electronic)&#xD;0014-2999 (Linking)</isbn><accession-num>28433657</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28433657</url></related-urls></urls><electronic-resource-num>10.1016/j.ejphar.2017.04.023</electronic-resource-num></record></Cite><Cite><Author>Liao</Author><Year>2016</Year><RecNum>141</RecNum><record><rec-number>141</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">141</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liao, Y.</author><author>Deng, Y.</author><author>Liu, J.</author><author>Ye, Z.</author><author>You, Z.</author><author>Yao, S.</author><author>He, S.</author></authors></contributors><auth-address>Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, PR China.&#xD;Department of Function, Hospital of Dongkeng, Dongguan 523451,PR China.&#xD;Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, PR China. Electronic address: hsy5g777@sina.com.</auth-address><titles><title>MiR-760 overexpression promotes proliferation in ovarian cancer by downregulation of PHLPP2 expression</title><secondary-title>Gynecol Oncol</secondary-title><alt-title>Gynecologic oncology</alt-title></titles><periodical><full-title>Gynecol Oncol</full-title><abbr-1>Gynecologic oncology</abbr-1></periodical><alt-periodical><full-title>Gynecol Oncol</full-title><abbr-1>Gynecologic oncology</abbr-1></alt-periodical><pages>655-663</pages><volume>143</volume><number>3</number><keywords><keyword>Blotting, Western</keyword><keyword>Carcinogenesis/genetics</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Proliferation/*genetics</keyword><keyword>Down-Regulation</keyword><keyword>Female</keyword><keyword>*Gene Expression Regulation, Neoplastic</keyword><keyword>HEK293 Cells</keyword><keyword>Humans</keyword><keyword>In Vitro Techniques</keyword><keyword>MicroRNAs/*genetics</keyword><keyword>Ovarian Neoplasms/*genetics/metabolism</keyword><keyword>Phosphoprotein Phosphatases/*metabolism</keyword><keyword>Real-Time Polymerase Chain Reaction</keyword><keyword>Up-Regulation</keyword></keywords><dates><year>2016</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1095-6859 (Electronic)&#xD;0090-8258 (Linking)</isbn><accession-num>27726922</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/27726922</url></related-urls></urls><electronic-resource-num>10.1016/j.ygyno.2016.09.010</electronic-resource-num></record></Cite><Cite><Author>Deng</Author><Year>2016</Year><RecNum>16</RecNum><record><rec-number>16</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1525968162">16</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Deng, J.</author><author>Ma, M.</author><author>Jiang, W.</author><author>Zhang, H.</author><author>Cui, S.</author></authors></contributors><titles><title>MiR-493 contributes to the proliferation and cell cycle in prostate cancer cells by repressing PHLPP2</title></titles><pages>15728-15736</pages><volume>9</volume><dates><year>2016</year></dates><urls></urls></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Ding</Author><Year>2017</Year><RecNum>139</RecNum><DisplayText>[402-406]</DisplayText><record><rec-number>139</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">139</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ding, L.</author><author>Zhang, S.</author><author>Xu, M.</author><author>Zhang, R.</author><author>Sui, P.</author><author>Yang, Q.</author></authors></contributors><auth-address>Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin Province, China.&#xD;Department of Orthopedics, The Second Hospital, Jilin University, Changchun, Jilin, China.&#xD;Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin Province, China. yangq@jlu.edu.cn.</auth-address><titles><title>MicroRNA-27a contributes to the malignant behavior of gastric cancer cells by directly targeting PH domain and leucine-rich repeat protein phosphatase 2</title><secondary-title>J Exp Clin Cancer Res</secondary-title><alt-title>Journal of experimental &amp; clinical cancer research : CR</alt-title></titles><periodical><full-title>J Exp Clin Cancer Res</full-title><abbr-1>Journal of experimental &amp; clinical cancer research : CR</abbr-1></periodical><alt-periodical><full-title>J Exp Clin Cancer Res</full-title><abbr-1>Journal of experimental &amp; clinical cancer research : CR</abbr-1></alt-periodical><pages>45</pages><volume>36</volume><number>1</number><dates><year>2017</year><pub-dates><date>Mar 21</date></pub-dates></dates><isbn>1756-9966 (Electronic)&#xD;0392-9078 (Linking)</isbn><accession-num>28327189</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28327189</url></related-urls></urls><custom2>5361803</custom2><electronic-resource-num>10.1186/s13046-017-0516-2</electronic-resource-num></record></Cite><Cite><Author>Mao</Author><Year>2015</Year><RecNum>143</RecNum><record><rec-number>143</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">143</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mao, X. P.</author><author>Zhang, L. S.</author><author>Huang, B.</author><author>Zhou, S. Y.</author><author>Liao, J.</author><author>Chen, L. W.</author><author>Qiu, S. P.</author><author>Chen, J. X.</author></authors></contributors><auth-address>Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. mxpzc1979@163.com.&#xD;Oncology Department, PLA458 Hospital, Guangzhou, 510000, China. lawysun@163.com.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. huangbin2007@yahoo.com.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. zhoushying@yeah.net.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. junliaogz@163.com.&#xD;Oncology Department, PLA458 Hospital, Guangzhou, 510000, China. lingwuch@126.com.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. qiushp@mail.sysu.edu.cn.&#xD;Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, PR China. chenjunxindoctor@163.com.</auth-address><titles><title>Mir-135a enhances cellular proliferation through post-transcriptionally regulating PHLPP2 and FOXO1 in human bladder cancer</title><secondary-title>J Transl Med</secondary-title><alt-title>Journal of translational medicine</alt-title></titles><periodical><full-title>J Transl Med</full-title><abbr-1>Journal of translational medicine</abbr-1></periodical><alt-periodical><full-title>J Transl Med</full-title><abbr-1>Journal of translational medicine</abbr-1></alt-periodical><pages>86</pages><volume>13</volume><keywords><keyword>Base Sequence</keyword><keyword>Cell Cycle/genetics</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Proliferation</keyword><keyword>Cyclin D1/metabolism</keyword><keyword>Cyclin-Dependent Kinase Inhibitor p21/metabolism</keyword><keyword>Cyclin-Dependent Kinase Inhibitor p27/metabolism</keyword><keyword>Forkhead Box Protein O1</keyword><keyword>Forkhead Transcription Factors/*genetics/metabolism</keyword><keyword>*Gene Expression Regulation, Neoplastic</keyword><keyword>Humans</keyword><keyword>Ki-67 Antigen/metabolism</keyword><keyword>MicroRNAs/genetics/*metabolism</keyword><keyword>Models, Biological</keyword><keyword>Molecular Sequence Data</keyword><keyword>Phosphoprotein Phosphatases/*genetics/metabolism</keyword><keyword>*Transcription, Genetic</keyword><keyword>Urinary Bladder Neoplasms/*genetics/*pathology</keyword></keywords><dates><year>2015</year><pub-dates><date>Mar 13</date></pub-dates></dates><isbn>1479-5876 (Electronic)&#xD;1479-5876 (Linking)</isbn><accession-num>25888950</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25888950</url></related-urls></urls><custom2>4367980</custom2><electronic-resource-num>10.1186/s12967-015-0438-8</electronic-resource-num></record></Cite><Cite><Author>Li</Author><Year>2017</Year><RecNum>137</RecNum><record><rec-number>137</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">137</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Li, C. F.</author><author>Li, Y. C.</author><author>Jin, J. P.</author><author>Yan, Z. K.</author><author>Li, D. D.</author></authors></contributors><auth-address>Department of Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun 130033, China.&#xD;Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China. Electronic address: yongchaolijl@163.com.</auth-address><titles><title>miR-938 promotes colorectal cancer cell proliferation via targeting tumor suppressor PHLPP2</title><secondary-title>Eur J Pharmacol</secondary-title><alt-title>European journal of pharmacology</alt-title></titles><periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></periodical><alt-periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></alt-periodical><pages>168-173</pages><volume>807</volume><dates><year>2017</year><pub-dates><date>Jul 15</date></pub-dates></dates><isbn>1879-0712 (Electronic)&#xD;0014-2999 (Linking)</isbn><accession-num>28433657</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28433657</url></related-urls></urls><electronic-resource-num>10.1016/j.ejphar.2017.04.023</electronic-resource-num></record></Cite><Cite><Author>Liao</Author><Year>2016</Year><RecNum>141</RecNum><record><rec-number>141</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">141</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liao, Y.</author><author>Deng, Y.</author><author>Liu, J.</author><author>Ye, Z.</author><author>You, Z.</author><author>Yao, S.</author><author>He, S.</author></authors></contributors><auth-address>Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, PR China.&#xD;Department of Function, Hospital of Dongkeng, Dongguan 523451,PR China.&#xD;Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, PR China. Electronic address: hsy5g777@sina.com.</auth-address><titles><title>MiR-760 overexpression promotes proliferation in ovarian cancer by downregulation of PHLPP2 expression</title><secondary-title>Gynecol Oncol</secondary-title><alt-title>Gynecologic oncology</alt-title></titles><periodical><full-title>Gynecol Oncol</full-title><abbr-1>Gynecologic oncology</abbr-1></periodical><alt-periodical><full-title>Gynecol Oncol</full-title><abbr-1>Gynecologic oncology</abbr-1></alt-periodical><pages>655-663</pages><volume>143</volume><number>3</number><keywords><keyword>Blotting, Western</keyword><keyword>Carcinogenesis/genetics</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Proliferation/*genetics</keyword><keyword>Down-Regulation</keyword><keyword>Female</keyword><keyword>*Gene Expression Regulation, Neoplastic</keyword><keyword>HEK293 Cells</keyword><keyword>Humans</keyword><keyword>In Vitro Techniques</keyword><keyword>MicroRNAs/*genetics</keyword><keyword>Ovarian Neoplasms/*genetics/metabolism</keyword><keyword>Phosphoprotein Phosphatases/*metabolism</keyword><keyword>Real-Time Polymerase Chain Reaction</keyword><keyword>Up-Regulation</keyword></keywords><dates><year>2016</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1095-6859 (Electronic)&#xD;0090-8258 (Linking)</isbn><accession-num>27726922</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/27726922</url></related-urls></urls><electronic-resource-num>10.1016/j.ygyno.2016.09.010</electronic-resource-num></record></Cite><Cite><Author>Deng</Author><Year>2016</Year><RecNum>16</RecNum><record><rec-number>16</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1525968162">16</key></foreign-keys><ref-type name="Book">6</ref-type><contributors><authors><author>Deng, J.</author><author>Ma, M.</author><author>Jiang, W.</author><author>Zhang, H.</author><author>Cui, S.</author></authors></contributors><titles><title>MiR-493 contributes to the proliferation and cell cycle in prostate cancer cells by repressing PHLPP2</title></titles><pages>15728-15736</pages><volume>9</volume><dates><year>2016</year></dates><urls></urls></record></Cite></EndNote>  ADDIN EN.CITE.DATA 402-406. Further, ectopic expression of miR-181a and miR-181d promoted S-phase entry and cell proliferation in luminal breast cancer cells through the suppression of PHLPP2 and INPP4B phosphatases expression thereby leading to hyperactivity of Akt 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 407. On the other hand, ectopic expression of miR-181b improved glucose homeostasis and insulin sensitivity in endothelial cells of adipose tissue in obese mice by suppressing the PHLPP2 expression 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 408.In a clinical study, Pan and colleagues noted that the transcript of PHLPP1 and PHLPP2 were reduced in 138 patients with squamous cell carcinoma which positioned PHLPP as independent prognostic markers 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ADDIN EN.CITE.DATA 409. Further studying the detailed molecular events in SCC, Xiaoyan et al. established that the upregulation of miR-224 targets 3’UTR of PHLPP1 and PHLPP2, suppressing protein expression. Cellular signalling analysis in ectopic miR-224 expression revealed PHLPP depleted enhanced Akt activity which promotes proliferation, migration, and invasion of SCC under cellular conditions 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ADDIN EN.CITE.DATA 410. Collectively PHLPP participates in diverse cellular activities to exhibit their antitumor and metastasis suppressor functions. A complete list of the all the miRNA and their targets (PHLPP1/2) under different pathological conditions are shown in the table.Table: List of miRNAs regulating the expression of PHLPP isozymes under diverse pathological conditions:miRNA PHLPP isozyme Functions ReferencesmiR-17-92 PHLPP2 human mantle cell lymphoma, acute myeloid leukemia ADDIN EN.CITE <EndNote><Cite><Author>Jiang</Author><Year>2010</Year><RecNum>131</RecNum><DisplayText>391</DisplayText><record><rec-number>131</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>131</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Jiang, P.</author><author>Rao, E. Y.</author><author>Meng, N.</author><author>Zhao, Y.</author><author>Wang, J. J.</author></authors></contributors><auth-address>Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China.</auth-address><titles><title>MicroRNA-17-92 significantly enhances radioresistance in human mantle cell lymphoma cells</title><secondary-title>Radiat Oncol</secondary-title><alt-title>Radiation oncology</alt-title></titles><periodical><full-title>Radiat Oncol</full-title><abbr-1>Radiation oncology</abbr-1></periodical><alt-periodical><full-title>Radiat Oncol</full-title><abbr-1>Radiation oncology</abbr-1></alt-periodical><pages>100</pages><volume>5</volume><keywords><keyword>Apoptosis/genetics/radiation effects</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Proliferation/radiation effects</keyword><keyword>Cell Separation</keyword><keyword>Flow Cytometry</keyword><keyword>Gene Expression/radiation effects</keyword><keyword>Humans</keyword><keyword>Immunoblotting</keyword><keyword>Lymphoma, Mantle-Cell/*genetics/*radiotherapy</keyword><keyword>MicroRNAs/*genetics</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Radiation Tolerance/*genetics</keyword><keyword>Transfection</keyword></keywords><dates><year>2010</year><pub-dates><date>Nov 01</date></pub-dates></dates><isbn>1748-717X (Electronic) 1748-717X (Linking)</isbn><accession-num>21040528</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21040528</url></related-urls></urls><custom2>2984457</custom2><electronic-resource-num>10.1186/1748-717X-5-100</electronic-resource-num></record></Cite></EndNote>391, 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 392miR-190 arsenic induced carcinogenesis 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 393miR-331-3p PHLPP1 hepatocellular carcinoma 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 394miR-3127 PHLPP1/2 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 395miR-3117 PHLPPL 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 396miR-205 PHLPP2 non-small cell lung cancer 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 397miR-141 PHLPP1/2 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 398miR-522 PHLPP1 human glioblastoma 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 400miR-372 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 401miR-27a gastric cancer ADDIN EN.CITE <EndNote><Cite><Author>Ding</Author><Year>2017</Year><RecNum>139</RecNum><DisplayText>402</DisplayText><record><rec-number>139</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>139</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ding, L.</author><author>Zhang, S.</author><author>Xu, M.</author><author>Zhang, R.</author><author>Sui, P.</author><author>Yang, Q.</author></authors></contributors><auth-address>Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin Province, China. Department of Orthopedics, The Second Hospital, Jilin University, Changchun, Jilin, China. Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin Province, China. [email protected].</auth-address><titles><title>MicroRNA-27a contributes to the malignant behavior of gastric cancer cells by directly targeting PH domain and leucine-rich repeat protein phosphatase 2</title><secondary-title>J Exp Clin Cancer Res</secondary-title><alt-title>Journal of experimental & clinical cancer research : CR</alt-title></titles><periodical><full-title>J Exp Clin Cancer Res</full-title><abbr-1>Journal of experimental & clinical cancer research : CR</abbr-1></periodical><alt-periodical><full-title>J Exp Clin Cancer Res</full-title><abbr-1>Journal of experimental & clinical cancer research : CR</abbr-1></alt-periodical><pages>45</pages><volume>36</volume><number>1</number><dates><year>2017</year><pub-dates><date>Mar 21</date></pub-dates></dates><isbn>1756-9966 (Electronic) 0392-9078 (Linking)</isbn><accession-num>28327189</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28327189</url></related-urls></urls><custom2>5361803</custom2><electronic-resource-num>10.1186/s13046-017-0516-2</electronic-resource-num></record></Cite></EndNote>402miR-493 prostate cancer ADDIN EN.CITE <EndNote><Cite><Author>Deng</Author><Year>2016</Year><RecNum>16</RecNum><DisplayText>406</DisplayText><record><rec-number>16</rec-number><foreign-keys><key app=”EN” db-id=”ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv” timestamp=”1525968162″>16</key></foreign-keys><ref-type name=”Book”>6</ref-type><contributors><authors><author>Deng, J.</author><author>Ma, M.</author><author>Jiang, W.</author><author>Zhang, H.</author><author>Cui, S.</author></authors></contributors><titles><title>MiR-493 contributes to the proliferation and cell cycle in prostate cancer cells by repressing PHLPP2</title></titles><pages>15728-15736</pages><volume>9</volume><dates><year>2016</year></dates><urls></urls></record></Cite></EndNote>406miR-135a bladder cancer 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 403miR-938 colorectal cancer ADDIN EN.CITE <EndNote><Cite><Author>Li</Author><Year>2017</Year><RecNum>137</RecNum><DisplayText>404</DisplayText><record><rec-number>137</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>137</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Li, C. F.</author><author>Li, Y. C.</author><author>Jin, J. P.</author><author>Yan, Z. K.</author><author>Li, D. D.</author></authors></contributors><auth-address>Department of Endoscopy Center, China-Japan Union Hospital, Jilin University, Changchun 130033, China. Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China. Electronic address: [email protected].</auth-address><titles><title>miR-938 promotes colorectal cancer cell proliferation via targeting tumor suppressor PHLPP2</title><secondary-title>Eur J Pharmacol</secondary-title><alt-title>European journal of pharmacology</alt-title></titles><periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></periodical><alt-periodical><full-title>Eur J Pharmacol</full-title><abbr-1>European journal of pharmacology</abbr-1></alt-periodical><pages>168-173</pages><volume>807</volume><dates><year>2017</year><pub-dates><date>Jul 15</date></pub-dates></dates><isbn>1879-0712 (Electronic) 0014-2999 (Linking)</isbn><accession-num>28433657</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28433657</url></related-urls></urls><electronic-resource-num>10.1016/j.ejphar.2017.04.023</electronic-resource-num></record></Cite></EndNote>404miR-760 ovarian cancer 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 407miR-181d miR-224 PHLPP1/2 squamous cell carcinoma 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 410miR-181b PHLPP2 improves glucose homeostasis in adipose tissue 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 408In addition to the miRNAs, another class of non-coding RNAs, the small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) are also reported to regulate the PHLPP expression. SNORA74B is upregulated in patients with gallbladder cancer (GBC) and was negatively correlated with expression of PHLPP1. Silencing SNORA74B enhanced the expression of PHLPP1 which results in suppressed activation of AKT/mTOR pathway. Interestingly, silencing PHLPP1 in SNORA74B overexpressing cells diminished the anti-tumor activity of SNORA74B 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ADDIN EN.CITE.DATA 411. However, the underlying molecular mechanism of SNORA74B–dependent regulation of PHLPP1 expression is still unknown. There are several reports describing the regulation of PHLPP and PTEN expression by numerous miRNA including miR17-92 cluster. While studying the role of PTENP1, a pseudogene, in hepatocarcinoma, Chen et al. reported that PTENP1 enhances PHLPP and PTEN expression. Using Sleeping Beauty (SB)-based hybrid baculovirus (BV) infectious system, they have shown that PTENP1 decoyed oncomiRs like miR-17, miR19b and miR 20a which would have otherwise targeted PHLPP and PTEN 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 412. Similarly, while studying the impact of Xist expression on breast cancer, it was observed that depletion of Xist expression inhibited Akt signaling via the upregulation of PHLPP1 expression ADDIN EN.CITE <EndNote><Cite><Author>Huang</Author><Year>2016</Year><RecNum>148</RecNum><DisplayText>413</DisplayText><record><rec-number>148</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>148</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Huang, Y. S.</author><author>Chang, C. C.</author><author>Lee, S. S.</author><author>Jou, Y. S.</author><author>Shih, H. M.</author></authors></contributors><auth-address>Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Graduate Institute of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.</auth-address><titles><title>Xist reduction in breast cancer upregulates AKT phosphorylation via HDAC3-mediated repression of PHLPP1 expression</title><secondary-title>Oncotarget</secondary-title><alt-title>Oncotarget</alt-title></titles><periodical><full-title>Oncotarget</full-title><abbr-1>Oncotarget</abbr-1></periodical><alt-periodical><full-title>Oncotarget</full-title><abbr-1>Oncotarget</abbr-1></alt-periodical><pages>43256-43266</pages><volume>7</volume><number>28</number><dates><year>2016</year><pub-dates><date>Jul 12</date></pub-dates></dates><isbn>1949-2553 (Electronic) 1949-2553 (Linking)</isbn><accession-num>27248326</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/27248326</url></related-urls></urls><custom2>5190021</custom2><electronic-resource-num>10.18632/oncotarget.9673</electronic-resource-num></record></Cite></EndNote>413. Further in-depth analysis identified that Xist assisted in recruiting SMRT co-repressor and HDAC3 complexes at PHLPP1 promoter for controlling its promoter activity. Further, a recent study identified direct correlation with lncRNA MEG3 and PHLPP1 expression in nickel associated malignant transformation of human bronchial epithelial cells. It was reported that the expression of MEG3 was diminished in dosed dependent manner of nickel exposure mediated by enhanced activity of DNMT3b 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ADDIN EN.CITE.DATA 390. Further the authors observed that MEG3 in complex with c-JUN, significantly impeded c-JUN transcriptional activity which enhanced PHLPP1 promoter activity and thus its expression to block the nickel induced oncogenic effect. The proposed mechanism appears to be specific as the expression and activity of other phosphatases like PHLPP2, PTEN and PP2A (A-C) where minimally modified.Translational Regulation:Regulation of protein translation (especially translational initiation) plays a prominent role in most processes in the cell and is one of the most critical steps in maintaining cellular homeostasis. Numerous clinical conditions arouse due aberrant regulation of protein biosynthesis, thus understanding the molecular basis and mechanisms of translational control is critical 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ADDIN EN.CITE.DATA 414, 415. New discoveries of the involvement of translational control in regulating cellular metabolism, proliferation and disease development are being published constantly. Activation of the PI3K/mTOR/Akt pathway by growth factors, hormones, and mitogen stimuli represents one of the major signal transduction cascades regulating global and specific mRNA translation ADDIN EN.CITE <EndNote><Cite><Author>Nandagopal</Author><Year>2015</Year><RecNum>150</RecNum><DisplayText>416</DisplayText><record><rec-number>150</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>150</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Nandagopal, N.</author><author>Roux, P. P.</author></authors></contributors><auth-address>Institute for Research in Immunology and Cancer (IRIC); Universite de Montreal ; Montreal, Quebec, Canada. Institute for Research in Immunology and Cancer (IRIC); Universite de Montreal; Montreal, Quebec, Canada; Department of Pathology and Cell Biology; Faculty of Medicine; Universite de Montreal; Montreal, Quebec, Canada.</auth-address><titles><title>Regulation of global and specific mRNA translation by the mTOR signaling pathway</title><secondary-title>Translation (Austin)</secondary-title><alt-title>Translation</alt-title></titles><periodical><full-title>Translation (Austin)</full-title><abbr-1>Translation</abbr-1></periodical><alt-periodical><full-title>Translation (Austin)</full-title><abbr-1>Translation</abbr-1></alt-periodical><pages>e983402</pages><volume>3</volume><number>1</number><dates><year>2015</year><pub-dates><date>Jan-Jun</date></pub-dates></dates><isbn>2169-074X (Print) 2169-0731 (Linking)</isbn><accession-num>26779414</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/26779414</url></related-urls></urls><custom2>4682803</custom2><electronic-resource-num>10.4161/21690731.2014.983402</electronic-resource-num></record></Cite></EndNote>416. Dysregulation of PI3K/Akt signalling is commonly associated with human diseases such as cancer and diabetes 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ADDIN EN.CITE.DATA 417, 418. Because the activity of Akt is tightly controlled by phosphorylation, direct dephosphorylation of Akt mediated by protein phosphatase namely PHLPP results in effective inactivation of the kinase. Hence, assessing the PHLPP translational control under pathological conditions like cancer, where the protein levels are abrogated, provides vital insights into the regulation the phosphatase.Preliminary studies by Gao’s group established that de novo protein synthesis of PHLPP appears to be regulated in part by the mammalian target of rapamycin complex 1 (mTORC1) activity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 419. Based on extensive cell-based studies using a panel of inhibitors as well as modulating the expression and activity of mTORC1, the authors reported that mTOR/TSC2/p70S6Kinase plays a dominant role in regulating PHLPP at the level of protein expression. Using a classical deprivation/re-introduction of amino acid (which is the upstream potent stimuli of mTOR activity) in culture conditions, authors established that physiological stimuli like amino acids and glucose exerts a potent regulation of PHLPP gene expression in mTORC1/S6Kinase dependent manner 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 419. However, the translational regulation of PHLPP1 is still obscure and demands a further in-depth investigation.Post-translational regulation:PHLPP was identified in the systematic search which can dephosphorylate Akt hydrophobic motif in regulating its activity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58. Akt serves as a central hub that transduces various extracellular cues to regulate a wide range of biological processes through phosphorylation of distinct protein substrates. During the past decade, most of the work has uncovered numerous other targets of PHLPP including PKC?II 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 59, however, there is a dearth of information about the post-translation modification of PHLPP which regulates its activity. Posttranslational modifications (PTM), such as phosphorylation, ubiquitination, sumoylation, and methylation, often regulate protein activity, localization, and stability.The preliminary observation that PTM plays an eminent role in PHLPP stability was reported by Shimizu et al. While elucidating the mechanism of circadian rhythm in rat suprachiasmatic nucleus they identified the protein SCOP (PHLPP1?). Mechanistic studies of the protein revealed that calpain catalyzes the calcium-sensitive proteolysis of PHLPP1? in neurons 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 369. Later, it was identified that PHLPP1 is a proteolytic target of ?TrCP. ?-TrCP is a subunit of the Skp-Cullin 1-F-box protein (SCF) ubiquitin E3 ligase complex which requires phosphorylation of its substrates to act on it. Detailed study by Gao’s lab identified that PHLPP was phosphorylated at multiple serine moieties by Casein Kinase I (at Ser867/Ser869) and glycogen synthase kinase 3beta (GSK-3beta) (at Ser847) to generate a docking site for ?-TrCP (DSG(X)2-nS (so-called “phospho-degron”)) for mediating ubiquitination and subsequent degradation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 420. Further, the interaction between PHLPP and ?-TrCP was noted to be strengthened by suppressor of G2 allele SKP1 (SGT1) in gastric cancer 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 421. SGT1 is known to be associated with SCF E3 ubiquitin ligase complex which mediates as co-chaperone in promoting the interaction between PHLPP and ?-TrCP resulting in degradation of PHLPP. Recently, while studying the role of emerging kinase GWL in human malignancies, Vera et al reported that overexpression of active GWL kinase depleted PHLPP protein level in GSK3? dependent manner 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 422. However, GWL failed to phosphorylate PHLPP and its correlation with GSK3? activity is still unidentified. A recent study suggested the role of free Raptor (unbound to mTOR complex) in the stability of PHLPP2 (and not PHLPP1) which prevents hepatic steatosis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 423. Molecular investigation under controlled overexpression of Raptor prevented ubiquitin-mediated degradation of PHLPP2 by hindering PHLPP2-?TrCP complex formation. Contradicting to the above observation, shRNA mediated depletion of Raptor and not Rictor showed a significant decrease in the PHLPP1 and PHLPP2 protein levels. The observed discrepancy could be due to following reason: 1) Difference in the cellular conditions. Kim et al pursued the study in liver cells, while Liu et al pursued their study in adenocarcinoma cells. The difference in the cellular origin and differential signalling patterns may have an impact on the interaction of the proteins. 2) Kim et al proposed that free Raptor plays a role in PHLPP2 stability, which is not bound to mTORC1 complex. It is important that Raptor interaction is very stringent with mTOR which is not dissociated even with treatment of Rapamycin (but it is enhanced under amino acid stimuli). Hence depleting Raptor expression may reduce free Raptor associated signalling cascade affecting PHLPP2 stability. Since ubiquitin-mediated degradation has emerged as one of the potent ways in controlling the PHLPP expression considerable research has also been emphasized in identifying the deubqituinatase regulating PHLPP turn over. Deubiquitinase, including ubiquitin-specific peptidase 1 (USP1) 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ADDIN EN.CITE.DATA 425 and USP46 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 426 have been shown to interact with and deubiquitinate PHLPP, resulting in increased protein stability, with certain discrepancies. Since these enzymes play a role in stabilizing PHLPP, a bonafide tumor suppressor, the protein levels and their corresponding activities of this deubiquitinase were noticed to be down-regulated in tumor development. Zhiqiang et al noted that PHLPP1 interacts with USP1 in NSCLC cells (A539) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 424. Using a series of biochemical and cell-based studies, it was established that USP1 interacts and deubiquitinates PHLPP1 which increases its half-life and thus protein stability. Similar to USP1, Li et al noted that PHLPP interacts with USP46 in colon cancer cells and stabilizes the protein 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 426. The ectopic interaction studies between PHLPP and USP1/USP46 was pursued in 293T cells. Contradicting to the above two observations, Maddika’s group noted that PHLPP failed to interact with USP1 and USP46 in 293T cells. They reported that WRD48-USP12 complex interacts with PHLPP and stabilizes it in colorectal cancer 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 425. The observed discrepancies in the PHLPP interactome demand further in-depth investigations. Similar to PHLPP1 expression regulated by ?-TrCP, a RING ubiquitin ligase, PHLPP2 expression was also regulated by KCTD17-CUL3. KCTD17 (potassium channel tetramerization domain containing 17 (KCTD17) is a substrate-adaptor for Cul3-RING ubiquitin ligases. To understand the endogenous regulatory machinery associated with PHLPP2 stability, Kim et al employed LC-MS/MS and identified novel glucagon/PKA mediated PHLPP2 phosphorylation at Ser 1119 and Ser1210. Phospho-modification of PHLPP2 by PKA augments its interaction with KCTD17 leading to its polyubiquitination mediated degradation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 427. It is well documented in the literature that post-translational modifications like phosphorylation events alter the protein catalytic activities. PHLPP, being a phosphatase, its enzymatic activity regulation by phosho-modification is still elusive. To date, only a sole report of Zhang et al. describing the association of Tyr phosphorylation of PHLPP with its enhanced activity upon insulin stimulation is reported 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 428. However, the mechanistic detail for this Tyr phosphorylation event is unknown. Further, GSK3? and CK1 mediated phosphorylation of PHLPP displayed minimal dephosphorylation activity of Akt 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 420. However, the aforesaid in vitro dephosphorylation study was pursued with truncated protein (PP2C domain only) and not full-length protein. Also, phosphomimetic mutants (Asp) and phospho-dead mutants (Ala) were used instead of more relevant in vitro phosphorylated protein for deciphering the impact of phosphorylation on PHLPP protein activity. Furthermore, the impact of PKA mediated PHLPP2 phosphorylation on its catalytic activity is still elusive 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 427. Altogether, based on the literature, impact of phospho-modification of PHLPP on its catalytic activity demands further investigation in deciphering the role of protein in numerous signalling circuits.1.7.4PHLPP in physiology and pathologyBy dephosphorylating its substrates, PHLPP controls numerous physiological processes; thus any alteration in its expression or functionality correlated with varied pathophysiological conditions. First identified as a tumour suppressor, it’s now known that modulation in PHLPP activity affect numerous other pathological conditions like insulin resistance, myocardial ischemia, and long-term memory formation. In our previous study, we have revealed a novel role of PHLPP1 in the regulation of macrophage-mediated inflammation. Below is the detailed discussion about the role of PHLPP in different pathological settings. Diseases associated with PHLPP ablation:PHLPP and Cancer: By suppressing cellular survival signalling circuits, PHLPP acts as an anti-tumorigenic protein that sensitizes cancer cells for chemotherapy <EndNote><Cite><Author>Chen</Author><Year>2011</Year><RecNum>492</RecNum><DisplayText>[356, 429-431]</DisplayText><record><rec-number>492</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">492</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chen, M.</author><author>Pratt, C. P.</author><author>Zeeman, M. E.</author><author>Schultz, N.</author><author>Taylor, B. S.</author><author>O&apos;Neill, A.</author><author>Castillo-Martin, M.</author><author>Nowak, D. G.</author><author>Naguib, A.</author><author>Grace, D. M.</author><author>Murn, J.</author><author>Navin, N.</author><author>Atwal, G. S.</author><author>Sander, C.</author><author>Gerald, W. L.</author><author>Cordon-Cardo, C.</author><author>Newton, A. C.</author><author>Carver, B. S.</author><author>Trotman, L. C.</author></authors></contributors><auth-address>Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.</auth-address><titles><title>Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression</title><secondary-title>Cancer Cell</secondary-title><alt-title>Cancer cell</alt-title></titles><periodical><full-title>Cancer Cell</full-title><abbr-1>Cancer cell</abbr-1></periodical><alt-periodical><full-title>Cancer Cell</full-title><abbr-1>Cancer cell</abbr-1></alt-periodical><pages>173-86</pages><volume>20</volume><number>2</number><keywords><keyword>Disease Progression</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>*Mutation</keyword><keyword>Nuclear Proteins/*physiology</keyword><keyword>PTEN Phosphohydrolase/*genetics/metabolism</keyword><keyword>Phosphoprotein Phosphatases/*physiology</keyword><keyword>Prostatic Neoplasms/metabolism/*pathology</keyword></keywords><dates><year>2011</year><pub-dates><date>Aug 16</date></pub-dates></dates><isbn>1878-3686 (Electronic)&#xD;1535-6108 (Linking)</isbn><accession-num>21840483</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21840483</url></related-urls></urls><custom2>3176728</custom2><electronic-resource-num>10.1016/j.ccr.2011.07.013</electronic-resource-num></record></Cite><Cite><Author>Pei</Author><Year>2009</Year><RecNum>111</RecNum><record><rec-number>111</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">111</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pei, H.</author><author>Li, L.</author><author>Fridley, B. L.</author><author>Jenkins, G. D.</author><author>Kalari, K. R.</author><author>Lingle, W.</author><author>Petersen, G.</author><author>Lou, Z.</author><author>Wang, L.</author></authors></contributors><auth-address>Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.</auth-address><titles><title>FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt</title><secondary-title>Cancer Cell</secondary-title><alt-title>Cancer cell</alt-title></titles><periodical><full-title>Cancer Cell</full-title><abbr-1>Cancer cell</abbr-1></periodical><alt-periodical><full-title>Cancer Cell</full-title><abbr-1>Cancer cell</abbr-1></alt-periodical><pages>259-66</pages><volume>16</volume><number>3</number><keywords><keyword>Antimetabolites, Antineoplastic/therapeutic use</keyword><keyword>Antineoplastic Agents/therapeutic use</keyword><keyword>Antineoplastic Agents, Phytogenic/therapeutic use</keyword><keyword>Cell Line</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cytarabine/therapeutic use</keyword><keyword>*Drug Therapy</keyword><keyword>Humans</keyword><keyword>Kidney/cytology</keyword><keyword>Neoplasms/*drug therapy/genetics/*metabolism/pathology</keyword><keyword>Nuclear Proteins/metabolism</keyword><keyword>Paclitaxel/therapeutic use</keyword><keyword>Pancreatic Neoplasms/genetics/metabolism</keyword><keyword>Phosphoprotein Phosphatases</keyword><keyword>Proto-Oncogene Proteins c-akt/isolation &amp; purification/*physiology</keyword><keyword>Tacrolimus Binding Proteins/*metabolism</keyword><keyword>Taxoids/therapeutic use</keyword></keywords><dates><year>2009</year><pub-dates><date>Sep 08</date></pub-dates></dates><isbn>1878-3686 (Electronic)&#xD;1535-6108 (Linking)</isbn><accession-num>19732725</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19732725</url></related-urls></urls><custom2>2755578</custom2><electronic-resource-num>10.1016/j.ccr.2009.07.016</electronic-resource-num></record></Cite><Cite><Author>Carver</Author><Year>2011</Year><RecNum>494</RecNum><record><rec-number>494</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">494</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Carver, B. S.</author><author>Chapinski, C.</author><author>Wongvipat, J.</author><author>Hieronymus, H.</author><author>Chen, Y.</author><author>Chandarlapaty, S.</author><author>Arora, V. K.</author><author>Le, C.</author><author>Koutcher, J.</author><author>Scher, H.</author><author>Scardino, P. T.</author><author>Rosen, N.</author><author>Sawyers, C. L.</author></authors></contributors><auth-address>Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.</auth-address><titles><title>Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer</title><secondary-title>Cancer Cell</secondary-title><alt-title>Cancer cell</alt-title></titles><periodical><full-title>Cancer Cell</full-title><abbr-1>Cancer cell</abbr-1></periodical><alt-periodical><full-title>Cancer Cell</full-title><abbr-1>Cancer cell</abbr-1></alt-periodical><pages>575-86</pages><volume>19</volume><number>5</number><keywords><keyword>Androgen Antagonists/pharmacology</keyword><keyword>Animals</keyword><keyword>Antineoplastic Combined Chemotherapy Protocols/pharmacology</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cell Proliferation/drug effects</keyword><keyword>Feedback, Physiological</keyword><keyword>Gene Expression Regulation, Neoplastic</keyword><keyword>Genes, Reporter</keyword><keyword>Humans</keyword><keyword>Magnetic Resonance Imaging</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, SCID</keyword><keyword>Mice, Transgenic</keyword><keyword>Nuclear Proteins/metabolism</keyword><keyword>PTEN Phosphohydrolase/*deficiency/genetics</keyword><keyword>Phosphatidylinositol 3-Kinase/antagonists &amp; inhibitors/*metabolism</keyword><keyword>Phosphoprotein Phosphatases/metabolism</keyword><keyword>Prostatic Neoplasms/drug therapy/*enzymology/genetics/pathology</keyword><keyword>Protein Kinase Inhibitors/pharmacology</keyword><keyword>Proto-Oncogene Proteins c-akt/antagonists &amp; inhibitors/metabolism</keyword><keyword>Proto-Oncogene Proteins c-myc/genetics/metabolism</keyword><keyword>RNA Interference</keyword><keyword>Receptor, ErbB-2/antagonists &amp; inhibitors/metabolism</keyword><keyword>Receptor, ErbB-3/antagonists &amp; inhibitors/metabolism</keyword><keyword>Receptors, Androgen/drug effects/*metabolism</keyword><keyword>*Signal Transduction/drug effects</keyword><keyword>Time Factors</keyword><keyword>Transcription, Genetic</keyword><keyword>Transfection</keyword><keyword>Tumor Burden/drug effects</keyword><keyword>Xenograft Model Antitumor Assays</keyword></keywords><dates><year>2011</year><pub-dates><date>May 17</date></pub-dates></dates><isbn>1878-3686 (Electronic)&#xD;1535-6108 (Linking)</isbn><accession-num>21575859</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21575859</url></related-urls></urls><custom2>3142785</custom2><electronic-resource-num>10.1016/j.ccr.2011.04.008</electronic-resource-num></record></Cite><Cite><Author>Mulholland</Author><Year>2011</Year><RecNum>495</RecNum><record><rec-number>495</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">495</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mulholland, D. J.</author><author>Tran, L. M.</author><author>Li, Y.</author><author>Cai, H.</author><author>Morim, A.</author><author>Wang, S.</author><author>Plaisier, S.</author><author>Garraway, I. P.</author><author>Huang, J.</author><author>Graeber, T. 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J.</author><author>Tran, L. M.</author><author>Li, Y.</author><author>Cai, H.</author><author>Morim, A.</author><author>Wang, S.</author><author>Plaisier, S.</author><author>Garraway, I. P.</author><author>Huang, J.</author><author>Graeber, T. G.</author><author>Wu, H.</author></authors></contributors><auth-address>Department of Molecular and Medical Pharmacology and Institute for Molecular Medicine, School of Medicine, University of California, Los Angeles, CA 90095-1735, USA.</auth-address><titles><title>Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth</title><secondary-title>Cancer Cell</secondary-title><alt-title>Cancer cell</alt-title></titles><periodical><full-title>Cancer Cell</full-title><abbr-1>Cancer cell</abbr-1></periodical><alt-periodical><full-title>Cancer Cell</full-title><abbr-1>Cancer cell</abbr-1></alt-periodical><pages>792-804</pages><volume>19</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Early Growth Response Protein 1/genetics</keyword><keyword>Enhancer of Zeste Homolog 2 Protein</keyword><keyword>Female</keyword><keyword>Histone-Lysine N-Methyltransferase/genetics</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Nuclear Proteins/physiology</keyword><keyword>*Orchiectomy</keyword><keyword>PTEN Phosphohydrolase/*physiology</keyword><keyword>Phosphoprotein Phosphatases/physiology</keyword><keyword>Phosphorylation</keyword><keyword>Polycomb Repressive Complex 2</keyword><keyword>Prostatic Neoplasms/etiology/*pathology/prevention &amp; control/therapy</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword><keyword>Proto-Oncogene Proteins c-jun/genetics</keyword><keyword>Receptors, Androgen/physiology</keyword><keyword>Tacrolimus Binding Proteins/physiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Jun 14</date></pub-dates></dates><isbn>1878-3686 (Electronic)&#xD;1535-6108 (Linking)</isbn><accession-num>21620777</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21620777</url></related-urls></urls><custom2>3157296</custom2><electronic-resource-num>10.1016/j.ccr.2011.05.006</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 356, 429-431. Several lines of pieces of evidence confirm the anti-tumorigenic role of PHLPP ADDIN EN.CITE <EndNote><Cite><Author>Grzechnik</Author><Year>2016</Year><RecNum>496</RecNum><DisplayText>432</DisplayText><record><rec-number>496</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>496</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Grzechnik, A. T.</author><author>Newton, A. C.</author></authors></contributors><auth-address>Biomedical Sciences Graduate Program, University of California at San Diego, La Jolla, CA 92093-0721, U.S.A. Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093-0721, U.S.A.</auth-address><titles><title>PHLPPing through history: a decade in the life of PHLPP phosphatases</title><secondary-title>Biochem Soc Trans</secondary-title><alt-title>Biochemical Society transactions</alt-title></titles><periodical><full-title>Biochem Soc Trans</full-title><abbr-1>Biochemical Society transactions</abbr-1></periodical><alt-periodical><full-title>Biochem Soc Trans</full-title><abbr-1>Biochemical Society transactions</abbr-1></alt-periodical><pages>1675-1682</pages><volume>44</volume><number>6</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus/genetics/metabolism</keyword><keyword>Gene Expression Regulation</keyword><keyword>Humans</keyword><keyword>Neoplasms/genetics/metabolism</keyword><keyword>Nuclear Proteins/genetics/*metabolism</keyword><keyword>Phosphoprotein Phosphatases/genetics/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Proto-Oncogene Proteins c-akt/*metabolism</keyword><keyword>*Signal Transduction</keyword></keywords><dates><year>2016</year><pub-dates><date>Dec 15</date></pub-dates></dates><isbn>1470-8752 (Electronic) 0300-5127 (Linking)</isbn><accession-num>27913677</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/27913677</url></related-urls></urls><custom2>5783572</custom2><electronic-resource-num>10.1042/BST20160170</electronic-resource-num></record></Cite></EndNote>432. A glance at the reported substrates of PHLPP including AKT 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58, PKC 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 59, ribosomal protein S6 kinase 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 366, Mst1 kinase 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 367 and RAF1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 372, displays clinically relevant oncogenic properties. Also, loss of PHLPP1 increases histone acetylation and phosphorylation resulting in enhanced gene expression of RTKs, such as EGFR 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 355, which is a well-established event associated with a plethora of human cancers. Thus, it is not surprising that PHLPPs are dysregulated in several human cancers like glioma, hypopharyngeal squamous cell carcinoma (HSCC) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 409, colon cancer 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 433, chronic myelogenous leukemia (CML) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 434, etc. Indeed, genetic loss of both the isozymes of PHLPP is detected in various types of cancers. Loss of heterozygosity of the genetic locus of PHLPP1 at 18q21.33 is reported in colon cancers 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 435, 436 and PHLPP2 at 16q22.3-16q23.1 in ovarian, prostate, breast, Wilms’ tumours, and hepatocellular carcinomas <EndNote><Cite><Author>Patael-Karasik</Author><Year>2000</Year><RecNum>28</RecNum><DisplayText>[437-441]</DisplayText><record><rec-number>28</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">28</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Patael-Karasik, Y.</author><author>Daniely, M.</author><author>Gotlieb, W. H.</author><author>Ben-Baruch, G.</author><author>Schiby, J.</author><author>Barakai, G.</author><author>Goldman, B.</author><author>Aviram, A.</author><author>Friedman, E.</author></authors></contributors><auth-address>Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel.</auth-address><titles><title>Comparative genomic hybridization in inherited and sporadic ovarian tumors in Israel</title><secondary-title>Cancer Genet Cytogenet</secondary-title></titles><periodical><full-title>Cancer Genet Cytogenet</full-title></periodical><pages>26-32</pages><volume>121</volume><number>1</number><edition>2000/08/26</edition><keywords><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>BRCA2 Protein</keyword><keyword>Chromosome Aberrations/*genetics</keyword><keyword>DNA/analysis/genetics</keyword><keyword>DNA, Neoplasm/analysis/genetics</keyword><keyword>Female</keyword><keyword>Gene Dosage</keyword><keyword>Genes, BRCA1/genetics</keyword><keyword>Heterozygote</keyword><keyword>Humans</keyword><keyword>Israel</keyword><keyword>Jews/genetics</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Mutation</keyword><keyword>Neoplasm Proteins/genetics</keyword><keyword>Nucleic Acid Hybridization</keyword><keyword>Ovarian Neoplasms/*genetics/pathology</keyword><keyword>Transcription Factors/genetics</keyword></keywords><dates><year>2000</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0165-4608 (Print)&#xD;0165-4608 (Linking)</isbn><accession-num>10958937</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10958937</url></related-urls></urls><electronic-resource-num>S0165-4608(00)00224-7 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Rakha</Author><Year>2006</Year><RecNum>24</RecNum><record><rec-number>24</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">24</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rakha, E. A.</author><author>Green, A. R.</author><author>Powe, D. G.</author><author>Roylance, R.</author><author>Ellis, I. O.</author></authors></contributors><auth-address>Department of Histopathology, the Breast Unit, Nottingham City Hospital NHS Trust and University of Nottingham, Nottingham, United Kingdom.</auth-address><titles><title>Chromosome 16 tumor-suppressor genes in breast cancer</title><secondary-title>Genes Chromosomes Cancer</secondary-title></titles><periodical><full-title>Genes Chromosomes Cancer</full-title></periodical><pages>527-35</pages><volume>45</volume><number>6</number><edition>2006/03/07</edition><keywords><keyword>Breast Neoplasms/*genetics</keyword><keyword>Chromosome Mapping</keyword><keyword>*Chromosomes, Human, Pair 16</keyword><keyword>Female</keyword><keyword>Genes, Overlapping</keyword><keyword>*Genes, Tumor Suppressor</keyword><keyword>Humans</keyword><keyword>Loss of Heterozygosity</keyword><keyword>Nucleic Acid Hybridization</keyword></keywords><dates><year>2006</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1045-2257 (Print)&#xD;1045-2257 (Linking)</isbn><accession-num>16518845</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16518845</url></related-urls></urls><electronic-resource-num>10.1002/gcc.20318</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Safford</Author><Year>2003</Year><RecNum>26</RecNum><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Safford, S. D.</author><author>Goyeau, D.</author><author>Freemerman, A. J.</author><author>Bentley, R.</author><author>Everett, M. L.</author><author>Grundy, P. E.</author><author>Skinner, M. A.</author></authors></contributors><auth-address>Department of Surgery, Division of Pediatric Surgery, Duke University Medical Center, Durham, North Carolina, USA.</auth-address><titles><title>Fine mapping of Wilms&apos; tumors with 16q loss of heterozygosity localizes the putative tumor suppressor gene to a region of 6.7 megabases</title><secondary-title>Ann Surg Oncol</secondary-title></titles><periodical><full-title>Ann Surg Oncol</full-title></periodical><pages>136-43</pages><volume>10</volume><number>2</number><edition>2003/03/07</edition><keywords><keyword>Cadherins/genetics</keyword><keyword>*Chromosomes, Human, Pair 16</keyword><keyword>Genes, Tumor Suppressor</keyword><keyword>*Genes, Wilms Tumor</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Immunoenzyme Techniques</keyword><keyword>Kidney Neoplasms/*genetics</keyword><keyword>*Loss of Heterozygosity</keyword><keyword>Microsatellite Repeats/genetics</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Statistics, Nonparametric</keyword><keyword>Wilms Tumor/*genetics</keyword></keywords><dates><year>2003</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1068-9265 (Print)&#xD;1068-9265 (Linking)</isbn><accession-num>12620908</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12620908</url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Torring</Author><Year>2007</Year><RecNum>27</RecNum><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Torring, N.</author><author>Borre, M.</author><author>Sorensen, K. D.</author><author>Andersen, C. L.</author><author>Wiuf, C.</author><author>Orntoft, T. F.</author></authors></contributors><auth-address>Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Skejby Sygehus, Aarhus University Hospital, Brendstrupgaardsvej 100, DK-8200 Aarhus, Denmark. nto@ki.au.dk</auth-address><titles><title>Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array</title><secondary-title>Br J Cancer</secondary-title></titles><periodical><full-title>Br J Cancer</full-title></periodical><pages>499-506</pages><volume>96</volume><number>3</number><edition>2007/01/25</edition><keywords><keyword>*Allelic Imbalance</keyword><keyword>DNA, Neoplasm/analysis</keyword><keyword>Gene Dosage</keyword><keyword>Genome, Human</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Loss of Heterozygosity</keyword><keyword>Male</keyword><keyword>Oligonucleotide Array Sequence Analysis/*methods</keyword><keyword>*Polymorphism, Single Nucleotide</keyword><keyword>Prostatic Neoplasms/*genetics/pathology</keyword></keywords><dates><year>2007</year><pub-dates><date>Feb 12</date></pub-dates></dates><isbn>0007-0920 (Print)&#xD;0007-0920 (Linking)</isbn><accession-num>17245344</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17245344</url></related-urls></urls><custom2>2360016</custom2><electronic-resource-num>6603476 [pii]&#xD;10.1038/sj.bjc.6603476</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Tsuda</Author><Year>1990</Year><RecNum>29</RecNum><record><rec-number>29</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">29</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tsuda, H.</author><author>Zhang, W. D.</author><author>Shimosato, Y.</author><author>Yokota, J.</author><author>Terada, M.</author><author>Sugimura, T.</author><author>Miyamura, T.</author><author>Hirohashi, S.</author></authors></contributors><auth-address>Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.</auth-address><titles><title>Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title></periodical><pages>6791-4</pages><volume>87</volume><number>17</number><edition>1990/09/01</edition><keywords><keyword>Alleles</keyword><keyword>Carcinoma, Hepatocellular/*genetics/pathology</keyword><keyword>Chromosome Deletion</keyword><keyword>Chromosome Mapping</keyword><keyword>*Chromosomes, Human, Pair 16</keyword><keyword>DNA Probes</keyword><keyword>DNA, Viral/isolation &amp; purification</keyword><keyword>Hepatitis B virus/isolation &amp; purification</keyword><keyword>Heterozygote</keyword><keyword>Humans</keyword><keyword>Liver/microbiology/pathology</keyword><keyword>Liver Cirrhosis/pathology</keyword><keyword>Liver Neoplasms/*genetics/pathology</keyword><keyword>Liver Regeneration</keyword><keyword>Models, Biological</keyword></keywords><dates><year>1990</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>2168560</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/2168560</url></related-urls></urls><custom2>54623</custom2><language>eng</language></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Patael-Karasik</Author><Year>2000</Year><RecNum>28</RecNum><DisplayText>[437-441]</DisplayText><record><rec-number>28</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">28</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Patael-Karasik, Y.</author><author>Daniely, M.</author><author>Gotlieb, W. H.</author><author>Ben-Baruch, G.</author><author>Schiby, J.</author><author>Barakai, G.</author><author>Goldman, B.</author><author>Aviram, A.</author><author>Friedman, E.</author></authors></contributors><auth-address>Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel.</auth-address><titles><title>Comparative genomic hybridization in inherited and sporadic ovarian tumors in Israel</title><secondary-title>Cancer Genet Cytogenet</secondary-title></titles><periodical><full-title>Cancer Genet Cytogenet</full-title></periodical><pages>26-32</pages><volume>121</volume><number>1</number><edition>2000/08/26</edition><keywords><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>BRCA2 Protein</keyword><keyword>Chromosome Aberrations/*genetics</keyword><keyword>DNA/analysis/genetics</keyword><keyword>DNA, Neoplasm/analysis/genetics</keyword><keyword>Female</keyword><keyword>Gene Dosage</keyword><keyword>Genes, BRCA1/genetics</keyword><keyword>Heterozygote</keyword><keyword>Humans</keyword><keyword>Israel</keyword><keyword>Jews/genetics</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Mutation</keyword><keyword>Neoplasm Proteins/genetics</keyword><keyword>Nucleic Acid Hybridization</keyword><keyword>Ovarian Neoplasms/*genetics/pathology</keyword><keyword>Transcription Factors/genetics</keyword></keywords><dates><year>2000</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0165-4608 (Print)&#xD;0165-4608 (Linking)</isbn><accession-num>10958937</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10958937</url></related-urls></urls><electronic-resource-num>S0165-4608(00)00224-7 [pii]</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Rakha</Author><Year>2006</Year><RecNum>24</RecNum><record><rec-number>24</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">24</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rakha, E. A.</author><author>Green, A. R.</author><author>Powe, D. G.</author><author>Roylance, R.</author><author>Ellis, I. O.</author></authors></contributors><auth-address>Department of Histopathology, the Breast Unit, Nottingham City Hospital NHS Trust and University of Nottingham, Nottingham, United Kingdom.</auth-address><titles><title>Chromosome 16 tumor-suppressor genes in breast cancer</title><secondary-title>Genes Chromosomes Cancer</secondary-title></titles><periodical><full-title>Genes Chromosomes Cancer</full-title></periodical><pages>527-35</pages><volume>45</volume><number>6</number><edition>2006/03/07</edition><keywords><keyword>Breast Neoplasms/*genetics</keyword><keyword>Chromosome Mapping</keyword><keyword>*Chromosomes, Human, Pair 16</keyword><keyword>Female</keyword><keyword>Genes, Overlapping</keyword><keyword>*Genes, Tumor Suppressor</keyword><keyword>Humans</keyword><keyword>Loss of Heterozygosity</keyword><keyword>Nucleic Acid Hybridization</keyword></keywords><dates><year>2006</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1045-2257 (Print)&#xD;1045-2257 (Linking)</isbn><accession-num>16518845</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16518845</url></related-urls></urls><electronic-resource-num>10.1002/gcc.20318</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Safford</Author><Year>2003</Year><RecNum>26</RecNum><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Safford, S. D.</author><author>Goyeau, D.</author><author>Freemerman, A. J.</author><author>Bentley, R.</author><author>Everett, M. L.</author><author>Grundy, P. E.</author><author>Skinner, M. A.</author></authors></contributors><auth-address>Department of Surgery, Division of Pediatric Surgery, Duke University Medical Center, Durham, North Carolina, USA.</auth-address><titles><title>Fine mapping of Wilms&apos; tumors with 16q loss of heterozygosity localizes the putative tumor suppressor gene to a region of 6.7 megabases</title><secondary-title>Ann Surg Oncol</secondary-title></titles><periodical><full-title>Ann Surg Oncol</full-title></periodical><pages>136-43</pages><volume>10</volume><number>2</number><edition>2003/03/07</edition><keywords><keyword>Cadherins/genetics</keyword><keyword>*Chromosomes, Human, Pair 16</keyword><keyword>Genes, Tumor Suppressor</keyword><keyword>*Genes, Wilms Tumor</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Immunoenzyme Techniques</keyword><keyword>Kidney Neoplasms/*genetics</keyword><keyword>*Loss of Heterozygosity</keyword><keyword>Microsatellite Repeats/genetics</keyword><keyword>Polymerase Chain Reaction</keyword><keyword>Statistics, Nonparametric</keyword><keyword>Wilms Tumor/*genetics</keyword></keywords><dates><year>2003</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1068-9265 (Print)&#xD;1068-9265 (Linking)</isbn><accession-num>12620908</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12620908</url></related-urls></urls><language>eng</language></record></Cite><Cite><Author>Torring</Author><Year>2007</Year><RecNum>27</RecNum><record><rec-number>27</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">27</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Torring, N.</author><author>Borre, M.</author><author>Sorensen, K. D.</author><author>Andersen, C. L.</author><author>Wiuf, C.</author><author>Orntoft, T. F.</author></authors></contributors><auth-address>Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Skejby Sygehus, Aarhus University Hospital, Brendstrupgaardsvej 100, DK-8200 Aarhus, Denmark. nto@ki.au.dk</auth-address><titles><title>Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array</title><secondary-title>Br J Cancer</secondary-title></titles><periodical><full-title>Br J Cancer</full-title></periodical><pages>499-506</pages><volume>96</volume><number>3</number><edition>2007/01/25</edition><keywords><keyword>*Allelic Imbalance</keyword><keyword>DNA, Neoplasm/analysis</keyword><keyword>Gene Dosage</keyword><keyword>Genome, Human</keyword><keyword>Genotype</keyword><keyword>Humans</keyword><keyword>Loss of Heterozygosity</keyword><keyword>Male</keyword><keyword>Oligonucleotide Array Sequence Analysis/*methods</keyword><keyword>*Polymorphism, Single Nucleotide</keyword><keyword>Prostatic Neoplasms/*genetics/pathology</keyword></keywords><dates><year>2007</year><pub-dates><date>Feb 12</date></pub-dates></dates><isbn>0007-0920 (Print)&#xD;0007-0920 (Linking)</isbn><accession-num>17245344</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17245344</url></related-urls></urls><custom2>2360016</custom2><electronic-resource-num>6603476 [pii]&#xD;10.1038/sj.bjc.6603476</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Tsuda</Author><Year>1990</Year><RecNum>29</RecNum><record><rec-number>29</rec-number><foreign-keys><key app="EN" db-id="ezs0pxta9ps0ahespzcxxwti092vxapt0r0f">29</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tsuda, H.</author><author>Zhang, W. D.</author><author>Shimosato, Y.</author><author>Yokota, J.</author><author>Terada, M.</author><author>Sugimura, T.</author><author>Miyamura, T.</author><author>Hirohashi, S.</author></authors></contributors><auth-address>Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.</auth-address><titles><title>Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma</title><secondary-title>Proc Natl Acad Sci U S A</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci U S A</full-title></periodical><pages>6791-4</pages><volume>87</volume><number>17</number><edition>1990/09/01</edition><keywords><keyword>Alleles</keyword><keyword>Carcinoma, Hepatocellular/*genetics/pathology</keyword><keyword>Chromosome Deletion</keyword><keyword>Chromosome Mapping</keyword><keyword>*Chromosomes, Human, Pair 16</keyword><keyword>DNA Probes</keyword><keyword>DNA, Viral/isolation &amp; purification</keyword><keyword>Hepatitis B virus/isolation &amp; purification</keyword><keyword>Heterozygote</keyword><keyword>Humans</keyword><keyword>Liver/microbiology/pathology</keyword><keyword>Liver Cirrhosis/pathology</keyword><keyword>Liver Neoplasms/*genetics/pathology</keyword><keyword>Liver Regeneration</keyword><keyword>Models, Biological</keyword></keywords><dates><year>1990</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0027-8424 (Print)&#xD;0027-8424 (Linking)</isbn><accession-num>2168560</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/2168560</url></related-urls></urls><custom2>54623</custom2><language>eng</language></record></Cite></EndNote>  ADDIN EN.CITE.DATA 437-441. Low levels of PHLPP1 expression is associated with recurrence and shorter overall survival time in sacral chordoma 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ADDIN EN.CITE.DATA 442 and lung adenocarcinoma patients 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 443. Thus, forced expression of PHLPP in several cancerous cell lines such as glioblastoma (GBM), colon cancer and pancreatic cancer decreased colony formation and growth in vitro as well as in xenograft models <EndNote><Cite><Author>Gao</Author><Year>2005</Year><RecNum>6</RecNum><DisplayText>[58, 365, 433]</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">6</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gao, T.</author><author>Furnari, F.</author><author>Newton, A. C.</author></authors></contributors><auth-address>Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA.</auth-address><titles><title>PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth</title><secondary-title>Mol Cell</secondary-title><alt-title>Molecular cell</alt-title></titles><periodical><full-title>Mol Cell</full-title><abbr-1>Molecular cell</abbr-1></periodical><alt-periodical><full-title>Mol Cell</full-title><abbr-1>Molecular cell</abbr-1></alt-periodical><pages>13-24</pages><volume>18</volume><number>1</number><keywords><keyword>Acid Phosphatase/chemistry/genetics/*metabolism</keyword><keyword>Amino Acid Sequence</keyword><keyword>Apoptosis</keyword><keyword>Cell Line</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cloning, Molecular</keyword><keyword>DNA, Complementary/genetics</keyword><keyword>Humans</keyword><keyword>Molecular Sequence Data</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Plasmids</keyword><keyword>Protein-Serine-Threonine Kinases/*metabolism</keyword><keyword>Proto-Oncogene Proteins/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Recombinant Fusion Proteins/chemistry/metabolism</keyword><keyword>Transfection</keyword></keywords><dates><year>2005</year><pub-dates><date>Apr 01</date></pub-dates></dates><isbn>1097-2765 (Print)&#xD;1097-2765 (Linking)</isbn><accession-num>15808505</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15808505</url></related-urls></urls><electronic-resource-num>10.1016/j.molcel.2005.03.008</electronic-resource-num></record></Cite><Cite><Author>Liu</Author><Year>2009</Year><RecNum>498</RecNum><record><rec-number>498</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">498</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu, J.</author><author>Weiss, H. L.</author><author>Rychahou, P.</author><author>Jackson, L. N.</author><author>Evers, B. M.</author><author>Gao, T.</author></authors></contributors><auth-address>Department of Biochemistry and Molecular Biology, West China Medical School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.</auth-address><titles><title>Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis</title><secondary-title>Oncogene</secondary-title><alt-title>Oncogene</alt-title></titles><periodical><full-title>Oncogene</full-title><abbr-1>Oncogene</abbr-1></periodical><alt-periodical><full-title>Oncogene</full-title><abbr-1>Oncogene</abbr-1></alt-periodical><pages>994-1004</pages><volume>28</volume><number>7</number><keywords><keyword>Animals</keyword><keyword>Blotting, Western</keyword><keyword>*Cell Proliferation</keyword><keyword>Colon/metabolism/pathology</keyword><keyword>Colorectal Neoplasms/*metabolism/pathology/prevention &amp; control</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunoenzyme Techniques</keyword><keyword>Lentivirus/genetics</keyword><keyword>Mice</keyword><keyword>Mice, Inbred BALB C</keyword><keyword>Mice, Nude</keyword><keyword>Nuclear Proteins/antagonists &amp; inhibitors/genetics/*metabolism</keyword><keyword>Phosphoprotein Phosphatases</keyword><keyword>Protein Isoforms</keyword><keyword>Protein Kinase C/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword><keyword>RNA, Small Interfering/pharmacology</keyword><keyword>Rectum/metabolism/pathology</keyword><keyword>Xenograft Model Antitumor Assays</keyword></keywords><dates><year>2009</year><pub-dates><date>Feb 19</date></pub-dates></dates><isbn>1476-5594 (Electronic)&#xD;0950-9232 (Linking)</isbn><accession-num>19079341</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19079341</url></related-urls></urls><custom2>2921630</custom2><electronic-resource-num>10.1038/onc.2008.450</electronic-resource-num></record></Cite><Cite><Author>Nitsche</Author><Year>2012</Year><RecNum>504</RecNum><record><rec-number>504</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">504</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nitsche, C.</author><author>Edderkaoui, M.</author><author>Moore, R. M.</author><author>Eibl, G.</author><author>Kasahara, N.</author><author>Treger, J.</author><author>Grippo, P. J.</author><author>Mayerle, J.</author><author>Lerch, M. M.</author><author>Gukovskaya, A. S.</author></authors></contributors><auth-address>Veterans Affairs Greater Los Angeles Healthcare System, University of California Los Angeles, Los Angeles, California, USA.</auth-address><titles><title>The phosphatase PHLPP1 regulates Akt2, promotes pancreatic cancer cell death, and inhibits tumor formation</title><secondary-title>Gastroenterology</secondary-title><alt-title>Gastroenterology</alt-title></titles><periodical><full-title>Gastroenterology</full-title><abbr-1>Gastroenterology</abbr-1></periodical><alt-periodical><full-title>Gastroenterology</full-title><abbr-1>Gastroenterology</abbr-1></alt-periodical><pages>377-87 e1-5</pages><volume>142</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>*Apoptosis</keyword><keyword>Carcinoma, Pancreatic Ductal/*enzymology/mortality</keyword><keyword>Humans</keyword><keyword>Kaplan-Meier Estimate</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Neoplasms, Experimental</keyword><keyword>Nuclear Proteins/*metabolism</keyword><keyword>Pancreatic Neoplasms/*enzymology/mortality</keyword><keyword>Phosphoprotein Phosphatases/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt/*metabolism</keyword><keyword>Tumor Cells, Cultured</keyword><keyword>Tumor Suppressor Proteins/metabolism</keyword></keywords><dates><year>2012</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1528-0012 (Electronic)&#xD;0016-5085 (Linking)</isbn><accession-num>22044669</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22044669</url></related-urls></urls><custom2>4545256</custom2><electronic-resource-num>10.1053/j.gastro.2011.10.026</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Gao</Author><Year>2005</Year><RecNum>6</RecNum><DisplayText>[58, 365, 433]</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">6</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gao, T.</author><author>Furnari, F.</author><author>Newton, A. C.</author></authors></contributors><auth-address>Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA.</auth-address><titles><title>PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth</title><secondary-title>Mol Cell</secondary-title><alt-title>Molecular cell</alt-title></titles><periodical><full-title>Mol Cell</full-title><abbr-1>Molecular cell</abbr-1></periodical><alt-periodical><full-title>Mol Cell</full-title><abbr-1>Molecular cell</abbr-1></alt-periodical><pages>13-24</pages><volume>18</volume><number>1</number><keywords><keyword>Acid Phosphatase/chemistry/genetics/*metabolism</keyword><keyword>Amino Acid Sequence</keyword><keyword>Apoptosis</keyword><keyword>Cell Line</keyword><keyword>Cell Line, Tumor</keyword><keyword>Cloning, Molecular</keyword><keyword>DNA, Complementary/genetics</keyword><keyword>Humans</keyword><keyword>Molecular Sequence Data</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Plasmids</keyword><keyword>Protein-Serine-Threonine Kinases/*metabolism</keyword><keyword>Proto-Oncogene Proteins/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt</keyword><keyword>Recombinant Fusion Proteins/chemistry/metabolism</keyword><keyword>Transfection</keyword></keywords><dates><year>2005</year><pub-dates><date>Apr 01</date></pub-dates></dates><isbn>1097-2765 (Print)&#xD;1097-2765 (Linking)</isbn><accession-num>15808505</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15808505</url></related-urls></urls><electronic-resource-num>10.1016/j.molcel.2005.03.008</electronic-resource-num></record></Cite><Cite><Author>Liu</Author><Year>2009</Year><RecNum>498</RecNum><record><rec-number>498</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">498</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Liu, J.</author><author>Weiss, H. L.</author><author>Rychahou, P.</author><author>Jackson, L. N.</author><author>Evers, B. M.</author><author>Gao, T.</author></authors></contributors><auth-address>Department of Biochemistry and Molecular Biology, West China Medical School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.</auth-address><titles><title>Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis</title><secondary-title>Oncogene</secondary-title><alt-title>Oncogene</alt-title></titles><periodical><full-title>Oncogene</full-title><abbr-1>Oncogene</abbr-1></periodical><alt-periodical><full-title>Oncogene</full-title><abbr-1>Oncogene</abbr-1></alt-periodical><pages>994-1004</pages><volume>28</volume><number>7</number><keywords><keyword>Animals</keyword><keyword>Blotting, Western</keyword><keyword>*Cell Proliferation</keyword><keyword>Colon/metabolism/pathology</keyword><keyword>Colorectal Neoplasms/*metabolism/pathology/prevention &amp; control</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Immunoenzyme Techniques</keyword><keyword>Lentivirus/genetics</keyword><keyword>Mice</keyword><keyword>Mice, Inbred BALB C</keyword><keyword>Mice, Nude</keyword><keyword>Nuclear Proteins/antagonists &amp; inhibitors/genetics/*metabolism</keyword><keyword>Phosphoprotein Phosphatases</keyword><keyword>Protein Isoforms</keyword><keyword>Protein Kinase C/metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword><keyword>RNA, Small Interfering/pharmacology</keyword><keyword>Rectum/metabolism/pathology</keyword><keyword>Xenograft Model Antitumor Assays</keyword></keywords><dates><year>2009</year><pub-dates><date>Feb 19</date></pub-dates></dates><isbn>1476-5594 (Electronic)&#xD;0950-9232 (Linking)</isbn><accession-num>19079341</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19079341</url></related-urls></urls><custom2>2921630</custom2><electronic-resource-num>10.1038/onc.2008.450</electronic-resource-num></record></Cite><Cite><Author>Nitsche</Author><Year>2012</Year><RecNum>504</RecNum><record><rec-number>504</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">504</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nitsche, C.</author><author>Edderkaoui, M.</author><author>Moore, R. M.</author><author>Eibl, G.</author><author>Kasahara, N.</author><author>Treger, J.</author><author>Grippo, P. J.</author><author>Mayerle, J.</author><author>Lerch, M. M.</author><author>Gukovskaya, A. S.</author></authors></contributors><auth-address>Veterans Affairs Greater Los Angeles Healthcare System, University of California Los Angeles, Los Angeles, California, USA.</auth-address><titles><title>The phosphatase PHLPP1 regulates Akt2, promotes pancreatic cancer cell death, and inhibits tumor formation</title><secondary-title>Gastroenterology</secondary-title><alt-title>Gastroenterology</alt-title></titles><periodical><full-title>Gastroenterology</full-title><abbr-1>Gastroenterology</abbr-1></periodical><alt-periodical><full-title>Gastroenterology</full-title><abbr-1>Gastroenterology</abbr-1></alt-periodical><pages>377-87 e1-5</pages><volume>142</volume><number>2</number><keywords><keyword>Animals</keyword><keyword>*Apoptosis</keyword><keyword>Carcinoma, Pancreatic Ductal/*enzymology/mortality</keyword><keyword>Humans</keyword><keyword>Kaplan-Meier Estimate</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Neoplasms, Experimental</keyword><keyword>Nuclear Proteins/*metabolism</keyword><keyword>Pancreatic Neoplasms/*enzymology/mortality</keyword><keyword>Phosphoprotein Phosphatases/*metabolism</keyword><keyword>Proto-Oncogene Proteins c-akt/*metabolism</keyword><keyword>Tumor Cells, Cultured</keyword><keyword>Tumor Suppressor Proteins/metabolism</keyword></keywords><dates><year>2012</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1528-0012 (Electronic)&#xD;0016-5085 (Linking)</isbn><accession-num>22044669</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22044669</url></related-urls></urls><custom2>4545256</custom2><electronic-resource-num>10.1053/j.gastro.2011.10.026</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 58, 365, 433. In U251 glioma cells overexpression of PHLPP inhibits expression of inflammatory cytokines like TNF-alpha, IL-17, and IL-1B, indicating a role of PHLPP1 in the suppression of the inflammatory response in human gliomas 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ADDIN EN.CITE.DATA 444. PHLPP also prevents dysregulation of glucose metabolism in colon cancer cells by inhibiting hexokinase-2 activity and thereby constraining the magnitude of glucose flux to the cancer cells ADDIN EN.CITE <EndNote><Cite><Author>Xiong</Author><Year>2017</Year><RecNum>77</RecNum><DisplayText>445</DisplayText><record><rec-number>77</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>77</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Xiong, X.</author><author>Wen, Y. A.</author><author>Mitov, M. I.</author><author>C. Oaks M</author><author>Miyamoto, S.</author><author>Gao, T.</author></authors></contributors><auth-address>Markey Cancer Center, University of Kentucky , Lexington, KY, USA. Department of Biology, University of Kentucky , Lexington, KY, USA. Department of Pharmacology, University of California, San Diego , La Jolla, CA, USA. Markey Cancer Center, University of Kentucky, Lexington, KY, USA; Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.</auth-address><titles><title>PHLPP regulates hexokinase 2-dependent glucose metabolism in colon cancer cells</title><secondary-title>Cell Death Discov</secondary-title><alt-title>Cell death discovery</alt-title></titles><periodical><full-title>Cell Death Discov</full-title><abbr-1>Cell death discovery</abbr-1></periodical><alt-periodical><full-title>Cell Death Discov</full-title><abbr-1>Cell death discovery</abbr-1></alt-periodical><pages>16103</pages><volume>3</volume><dates><year>2017</year></dates><isbn>2058-7716 (Print) 2058-7716 (Linking)</isbn><accession-num>28179998</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28179998</url></related-urls></urls><custom2>5253420</custom2><electronic-resource-num>10.1038/cddiscovery.2016.103</electronic-resource-num></record></Cite></EndNote>445. Further, PHLPP knockout mice displayed a higher incidence of intraepithelial neoplasia in prostate tissue, which eventually progressed to carcinoma upon partial loss of PTEN 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ADDIN EN.CITE.DATA 429. In addition to the direct loss of gene and/or loss of function of PHLPP, dysregulation of post-transcriptional, translational and scaffold protein interactions also results in down-regulation of PHLPP in cancer. In aggressive glioblastoma, the PTEN-NHERF1-PHLPP1 tumor suppressor network is significantly downregulated 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ADDIN EN.CITE.DATA 358 and the AKT mediated feedback inhibition of PHLPP1 is lost due to mislocalization of the -TrCP1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 446. Similarly, AKT-PHLPP scaffolding protein, FKBP51 is noticeably downregulated in pancreatic carcinoma and several other cancers, resulting in hyperactivation of Akt both in vitro 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 356, and in vivo 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 447. Several deubiquitinating enzymes were found to stabilize PHLPPs, thus loss of interaction with the deubiquitinases like USP12 in CRC (colorectal cancer) and USP46 in colon cancer cells results in downregulation of PHLPP1 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 425, 426. Several tumour promoting miRNAs are known to inhibit PHLPP in a number of carcinoma, including HCC (miR-331-3p and miR-3127 targeting 3′ UTR of PHLPP1 and PHLPP2 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 394, 395), non-small cell lung cancer (miR- 205 targeting 3′ UTR of PHLPP2 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ADDIN EN.CITE.DATA 397), gastric cancer (miR-27a, PHLPP2 ADDIN EN.CITE <EndNote><Cite><Author>Ding</Author><Year>2017</Year><RecNum>139</RecNum><DisplayText>402</DisplayText><record><rec-number>139</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>139</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ding, L.</author><author>Zhang, S.</author><author>Xu, M.</author><author>Zhang, R.</author><author>Sui, P.</author><author>Yang, Q.</author></authors></contributors><auth-address>Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin Province, China. Department of Orthopedics, The Second Hospital, Jilin University, Changchun, Jilin, China. Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin Province, China. [email protected].</auth-address><titles><title>MicroRNA-27a contributes to the malignant behavior of gastric cancer cells by directly targeting PH domain and leucine-rich repeat protein phosphatase 2</title><secondary-title>J Exp Clin Cancer Res</secondary-title><alt-title>Journal of experimental & clinical cancer research : CR</alt-title></titles><periodical><full-title>J Exp Clin Cancer Res</full-title><abbr-1>Journal of experimental & clinical cancer research : CR</abbr-1></periodical><alt-periodical><full-title>J Exp Clin Cancer Res</full-title><abbr-1>Journal of experimental & clinical cancer research : CR</abbr-1></alt-periodical><pages>45</pages><volume>36</volume><number>1</number><dates><year>2017</year><pub-dates><date>Mar 21</date></pub-dates></dates><isbn>1756-9966 (Electronic) 0392-9078 (Linking)</isbn><accession-num>28327189</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28327189</url></related-urls></urls><custom2>5361803</custom2><electronic-resource-num>10.1186/s13046-017-0516-2</electronic-resource-num></record></Cite></EndNote>402). Similar, small nucleolar RNA like SNORA74B, detected in gallbladder cancer (GBC), the expression is inversely proportional to the expression of PHLPP 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ADDIN EN.CITE.DATA 411. A detailed description of correlation between miRNA and PHLPP expression in cancer progression is discussed in section —–. Thus, the data above illustrate overwhelming evidence for the tumour suppressive roles of PHLPPs and suggests potentially activators of PHLPP as promising for clinical perspectives.PHLPP and inflammation:Earlier publications on PHLPP from our group talk about a unique immune-modulatory role of PHLPP1. Dysregulation of innate immune responses are frequently encountered in several cancers and PHLPP being an anti-tumorigenic protein was anticipated to have a role in governing immune responses. In the study, we observed a decrease in PHLPP1 expression both at mRNA and protein levels upon LPS treatment in immune cells. While forced expression of PHLPP1 in RAW 264.7 macrophages decreased LPS/IFN-?-induced iNOS expression via suppression of phosphorylation of STAT1ser727. However, the underlying molecular mechanism was stimuli specific. Upon IFN-? treatment PHLPP1 reduced ser727 STAT1 phosphorylation and iNOS expression via suppressing phosphorylation of ERK1/2, whereas upon LPS treatment PHLPP1 restricted LPS-stimulated phosphorylation of ser727 STAT1, iNOS expression by inhibiting p38 phosphorylation and restricted LPS-induced phosphorylation of tyr701 STAT1 by dampening p38-dependent IFN-? feedback ADDIN EN.CITE <EndNote><Cite><Author>Alamuru</Author><Year>2014</Year><RecNum>71</RecNum><DisplayText>371</DisplayText><record><rec-number>71</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>71</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Alamuru, N. P.</author><author>Behera, S.</author><author>Butchar, J. P.</author><author>Tridandapani, S.</author><author>Kaimal Suraj, S.</author><author>Babu, P. P.</author><author>Hasnain, S. E.</author><author>Ehtesham, N. Z.</author><author>Parsa, K. V.</author></authors></contributors><auth-address>Dr. Reddy's Institute of Life Sciences (DRILS), Hyderabad, India. Department of Biotechnology, University of Hyderabad, Hyderabad, India. Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA. Department of Biological Sciences, Indian Institute of Technology, New Delhi, India; and. National Institute of Pathology, Safdarjung Hospital, New Delhi, India. Dr. Reddy's Institute of Life Sciences (DRILS), Hyderabad, India; [email protected].</auth-address><titles><title>A novel immunomodulatory function of PHLPP1: inhibition of iNOS via attenuation of STAT1 ser727 phosphorylation in mouse macrophages</title><secondary-title>J Leukoc Biol</secondary-title><alt-title>Journal of leukocyte biology</alt-title></titles><periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></periodical><alt-periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></alt-periodical><pages>775-783</pages><volume>95</volume><number>5</number><dates><year>2014</year><pub-dates><date>May</date></pub-dates></dates><isbn>1938-3673 (Electronic) 0741-5400 (Linking)</isbn><accession-num>24443556</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24443556</url></related-urls></urls><electronic-resource-num>10.1189/jlb.0713360</electronic-resource-num></record></Cite></EndNote>371. Further, in the next study, we observed that the decreased transcript levels of PHLPP upon LPS treatment was due to reduced association of SP1 to the PHLPP promoter. Overexpression of SP1 enhanced both transcript and protein levels of PHLPP while, knockdown of SP1 or pharmacological inhibition of SP1 DNA binding by mithramycin reduced the expression of PHLPP1. In addition, SP1 driven PHLPP1 promoter activity was augmented upon forced expression of SP1 co-activators CBP/p300. Thus collectively the data shows PHLPP to be playing an important role in restricting innate immune responses of macrophages 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 389.PHLPP and T cell biology:Regulatory T cells (Tregs) are responsible for maintaining immune cell homeostasis by suppression of the immune response to self and nonharmful foreign proteins. The best characterised CD4+CD25+ Treg cells show decreased phosphorylation of AKT at Ser473 but not Thr308 and reduced activity of downstream effectors of AKT like FoxO and S6 kinase 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 448. This reduced activity of PI3K/AKT pathway due to specific dephosphorylation of Treg cells at AKT Ser473 is necessary for the suppressive function of CD4+CD25+ Treg cells and is achieved by upregulation of PHLPP1. Patterson et al observed a significant increase in the expression of both PHLPP1 and PHLPP2 in CD4+Foxp3+ T-cells isolated from mice and CD4+CD25 Tregs from Human PBMCs. Knock-down of PHLPP1 restores the activation of Akt in CD4+Foxp3+ T cells, while in human CD4+ T cells knockdown of both PHLPP1/2 is required to activate AKT. Unlike to PTEN-deficient Tregs, PHLPP1-deficient Tregs did not proliferate in response to IL-2 alone, indicating PHLPP1 is not required for Treg anergy but showed a significant decrease in suppressive capacity than the Treg from WT littermates. Further, expression of PHLPP, parallel with Foxp3, was enhanced upon TGF-? mediated development of induced-Tregs, while Tconvs isolated from PHLPP1-/- mice stimulated with TGF-? and IL-2 displayed reduced Foxp3 expression and mere absence iTreg development on knockdown of PHLPP2 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 387. However, PHLPP1-/- mice displayed the normal development of natural Tregs may be due to their lesser dependency on finely-tuned PI3K/AKT pathway for development than iTregs or PHLPP2 may compensate for PHLPP1 lose in these mice. Thus PHLPP acts as a key molecular regulator for restricting activation of AKT, required for the suppressive function and development of human Treg cells. Adversely for the development of TFH cells and germinal centre, activation of PIK/AKT pathway is needed.Diseases associated with upregulation of PHLPP:PHLPP and heart:The heart is equipped with extreme adaptive responses to maintain its contractile function. Although the heart may functionally tolerate a range of pathological insults, it eventually fails to maintain adaptive response, resulting in a wide array of functional deficits or cardiomyopathy. Akt, the major mediator of PI3K signalling, plays a vital role in cardiac adaptation including protein synthesis and metabolism. It is well known from numerous independent studies that activation of the PI3K/Akt pathway protects the heart from ischemia-reperfusion injury (IRI). Using a congenital model of PTEN haploinsufficiency mice model, Siddall et al. observed a significant decrease in the ischemic preconditioning threshold associated with enhanced phosphorylation of AKT. However, PTEN haploinsufficiency alone was not sufficient for cardioprotection, indicating that the activity of other PI3K negative regulators including PP2A, SHIP2, and PHLPP was critical for cardioprotection 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 449. While addressing the important question of crosstalk between adenyl cyclase 6 and enhanced pAKT in cardiomyocytes, it was noted that PHLPP2 expression was unaltered. RNAi mediated depletion of PHLPP2 partially restored pAkt levels in AC6 overexpressing cardiomyocytes treated with NKH-477. The authors proposed that PHLPP2 might interact with AC6 (adenylyl cyclase type 6) and regulate pAkt in cAMP/PKA independent manner via conformational change 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 450. However, the current study was not able to address certain critical observations. Firstly, the basal level of pAkt was enhanced upon overexpression of AC6 gene. Second and more important the expression of other phosphatases of PI3K signalling like PHLPP1, PP2A, and SHIP2 expression were not studied. Recently it was reported that sustained activity of adenyl cyclase in hepatocytes caused ubiquitin-mediated degradation of PHLPP2 (not PHLPP1) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 427. The observed discrepancy may be due to differences in the cellular origin; however, more in-depth studies are warranted to define the functional role of PHLPP2 in cardioprotection.In contrast to PHLPP2, PHLPP1 role in the regulation of cardiac activity is well established. Depleting PHLPP1 expression using siRNA in rat ventricular myocytes specifically stimulated the pAkt at Ser473 (and not Thr308) in presence of agonists like leukemia inhibitory factor (LIF), insulin-like growth factor-1, or sphingosine 1-phosphate; while the expression of LIF receptor was noticed unaffected with PHLPP1 depletion. Further, the authors observed enhanced phosphorylation of hexokinase-II upon agonist-induced mitochondrial targeting of Akt, which resulted in cell death during ischemia/reperfusion (I/R) due to inhibition of Ca2+-induced cytochrome c release, showing a direct role of PHLPP1 expression on mitochondrial perturbation and cell survival. However, PHLPP1 doesn’t affect nuclear targeting or expression of phospho-Akt in LIF-stimulated cells. Furthermore, using PHLPP1 conditional knockout mice, Miyamoto et al found a 45% reduction in myocardial infarct size, demonstrating the importance of regulation of PHLPP mediated Akt signalling in cardioprotection 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 451. Although the authors provide novel insights into the regulation of Akt mediated cardiomyopathy, there remain few unanswered questions. Firstly, the expression of PHLPP1 was unaltered under ischemia/reperfusion (I/R) stimulus, indicating the activity of PHLPP1 was enhanced to culminate the pAkt. Hence the upstream signalling circuits which regulate PHLPP1 activity under I/R needs to be deciphered to have a broad implication in cardioprotection. Also, mechanism of specificity displayed by PHLPP1 specifically targeted mitochondrial Akt activity, while nuclear Akt was unaltered, remains unanswered. It is highly possible that compartmentalization of signalling may play a vital role in Akt regulation. Feasibility is that nuclear Akt signalling may be regulated by PHLPP2 (and not by PHLPP1).Consistent with the previous report, Ma H and colleagues also noted that PHLPP1 plays a positive role in cardioprotection. With the aim to define the competitive interaction between insulin-stimulated Akt and PHLPP, young and aged rats were subjected to myocardial I/R (MI/R). An elevated level of PHLPP1 was detected in the heart of aged rat compared to the younger group, which impaired insulin-induced Akt mediated cardioprotection and enhanced the susceptible to MI/R injury in aged rats. When the aged rat was subjected to altered PHLPP-1 expression (knockdown and overexpression) or enhanced insulin sensitivity by exercise training, dramatically altered insulin-induced Akt phosphorylation and decreased MI/R-induced cardiomyocyte apoptosis and infarct size was observed resulting in improved cardiac functioning with a negative correlation of PHLPP expression. Further, in-depth analysis, it was noted that insulin depleted PHLPP protein levels through ?-TrCP mediated ubiquitin-mediated proteolytic degradation ADDIN EN.CITE <EndNote><Cite><Author>Xing</Author><Year>2016</Year><RecNum>24</RecNum><DisplayText>452</DisplayText><record><rec-number>24</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>24</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Xing, Y.</author><author>Sun, W.</author><author>Wang, Y.</author><author>Gao, F.</author><author>Ma, H.</author></authors></contributors><auth-address>Department of Physiology, Fourth Military Medical University, Xi'an 710032, China. Department of Cardiovascular Medicine, First Affiliated Hospital of Jilin University, Changchun 130000, China. Department of Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, China. Department of Pathophysiology, Fourth Military Medical University, Xi'an 710032, China.</auth-address><titles><title>Mutual inhibition of insulin signaling and PHLPP-1 determines cardioprotective efficiency of Akt in aged heart</title><secondary-title>Aging (Albany NY)</secondary-title><alt-title>Aging</alt-title></titles><periodical><full-title>Aging (Albany NY)</full-title><abbr-1>Aging</abbr-1></periodical><alt-periodical><full-title>Aging (Albany NY)</full-title><abbr-1>Aging</abbr-1></alt-periodical><pages>873-88</pages><volume>8</volume><number>5</number><dates><year>2016</year><pub-dates><date>May</date></pub-dates></dates><isbn>1945-4589 (Electronic) 1945-4589 (Linking)</isbn><accession-num>27019292</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/27019292</url></related-urls></urls><custom2>4931841</custom2><electronic-resource-num>10.18632/aging.100933</electronic-resource-num></record></Cite></EndNote>452. However, certain questions still remain unanswered such as what are the signalling events that are altered in aged mice which prevent insulin-stimulated PHLPP degradation? It is well established in the literature that exercise improves cardiac functionality in AMPK dependent manner, hence it will be interesting to examine if AMPK signalling plays any role in regulating PHLPP protein levels, as exercise is observed to diminish PHLPP protein levels.PHLPP and Osteoarthritis (OA):OA is characterized by articular chondrocyte deterioration and sub-chondral bone alterations associated with unbearable pain. Promotion of cartilage regeneration and repair resulting in better proliferation and matrix production of the articular chondrocytes is suggested to improve OA. PHLPP1 has reported to controls chondrocyte differentiation by regulating the activities of anabolic kinases. Ablation of PHLPP1 increases Akt2 activity, which diminishes FoxO1 levels and induces Fgf18 expression to stimulate Erk1/2 activity leading to chondrocyte proliferation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 361. Further, expression of PHLPP1 is reported to be augmented in human articular cartilage from OA patients 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 385, correlated with less CpG methylation of the PHLPP1 promoter 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 386. Deletion of Phlpp1 in the DMM mice model showed resistance to cartilage degeneration, mechanical allodynia and displayed thicker articular cartilage and more articular chondrocytes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 385. Hence, inhibition of PHLPP1 by deficiency by intra-articular injection of the Phlpp1/2 (NSC117079) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 359 inhibitor in surgically PTOA (post-traumatic osteoarthritis) induced mice attenuated mechanical allodynia and slowed articular cartilage degradation in osteoarthritic joints by stabilizing the phosphorylation of AKT2 and PKC, however, the underlying mechanistic details are yet to be elucidated 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 453. PHLPP and brain:Owing to the abundance of PHLPP isozymes expression in the brain, PHLPP is being attributed with several neural functions. PHLPP via restricting MAPK/ERK1/2 signalling plays a critical role in neuro-plasticity, especially in long-term memory consolidation. Forced expression of PHLPP1? in the murine forebrain completely blocked the formation of long?term novel object memory 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 369, while ablation of Phlpp1 protects neurons against ischemic insult in a mouse model of stroke by enhancing the activation of Akt in neurons and astrocytes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 454. Interestingly, compared to PTEN inhibitors, inhibition of Phlpp1 might be preferable as Phlpp1-deficient mice show only a slight change in brain size, and no evident brain cancers till date unlike to Pten-deficient neurons mouse models with macrocephaly, seizures, and autism-related disorders and a higher incidence of cancer 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 455, 456. Further, downregulation of PHLPP1 expression is observed in the striatum of huntingtin transgenic mouse models and in the putamen of Huntington’s patients. Suppression of PHLPP1 contributes to the higher levels of Akt activation that may retard cell death and salvage of neuronal activity upon silencing of mutant huntingtin 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 388.Although the mechanism is unclear, PHLPP1 is known to affect the light?induced resetting of the circadian clock 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 457. Mice lacking PHLPP1 fails to stabilize the circadian period after light-induced resetting, resulting in a large phase shift after light resetting. Interestingly, in-vivo infusion of PKC inhibitor, bisindolylmaleimide I, to the SCN (suprachiasmatic nucleus) markedly enhanced the phase-shifting effects of light 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 458, speculating a role of PHLPP mediated PKC inhibition in the proper functioning of the circadian clock. PHLPP & Insulin Resistance:Differential regulation of Akt isoforms by the PHLPP isozymes indicates towards the specificity of the phosphatase for its targets. Selective dephosphorylation of Akt2 by PHLPP1 in insulin-sensitive tissues like skeletal muscle and adipose pointed towards the potential role of PHLPP1 in insulin signalling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 347. A clinical report by Andreozzi et al shows two-fold enhanced expression of PHLPP1 in the subcutaneous fat and skeletal muscle samples of obese patients compared to the non-obese or lean participants, with no significant differences between obese participants with normal fasting glucose, impaired fasting glucose or T2D. Further, a dose- and time-dependent upregulation of PHLPP1 expression was detected upon stimulation with insulin in HepG2 cells. While forced expression of PHLPP1 in HepG2 cells and rat L6 myoblasts resulted in impaired the action of insulin namely glycogen synthesis and glucose transport, envisaging PHLPP1 as an unidentified molecular fault in insulin-resistant states such as obesity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 459. In a study conducted across multiple databases in order to identify genetic marker associated with T2D in populations living in Africa, polymorphisms in PHLPP1 gene was identified. Based on the above information, in past couple of years, several researchers opined their views positioning PHLPP phosphatase as an ideal therapeutic target in insulin resistance-related diseases, however a number of issues (as discussed concluding para of chapter 1.1.6.e) should be resolved before PHLPPs are pursued as therapeutic targets including the mechanisms regulating the expression as well as specificity of phosphatase in regulating insulin dependent as well insulin-independent glucose homeostasis. Chapter 2-5 RESULTS AND DISCUSSIONChapter-2 ER stress & inflammation mediate transcriptional augmentation of PHLPP1Key findings: The PHLPP1 expression is elevated in animals displaying insulin resistance Transcriptional upregulation of PHLPP1 is induced by inflammation and ER stressDepletion of PHLPP1 relieved ER stress induced by tunicamycin In type 2 diabetes mellitus, impairment of glucose uptake in skeletal muscle defines the state of insulin resistance ADDIN EN.CITE <EndNote><Cite><Author>Saltiel</Author><Year>2001</Year><RecNum>212</RecNum><DisplayText>117</DisplayText><record><rec-number>212</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>212</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Saltiel, A. R.</author></authors></contributors><auth-address>Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.</auth-address><titles><title>New perspectives into the molecular pathogenesis and treatment of type 2 diabetes</title><secondary-title>Cell</secondary-title><alt-title>Cell</alt-title></titles><periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></periodical><alt-periodical><full-title>Cell</full-title><abbr-1>Cell</abbr-1></alt-periodical><pages>517-29</pages><volume>104</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Blood Glucose/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/*etiology/genetics/*metabolism/physiopathology/*therapy</keyword><keyword>Glycogen/biosynthesis</keyword><keyword>Humans</keyword><keyword>Insulin/metabolism</keyword><keyword>Insulin Resistance</keyword><keyword>Islets of Langerhans/metabolism</keyword><keyword>Models, Biological</keyword><keyword>Obesity</keyword><keyword>Protein-Tyrosine Kinases/metabolism</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Receptors, Cytoplasmic and Nuclear/metabolism</keyword><keyword>Signal Transduction</keyword><keyword>Transcription Factors/metabolism</keyword></keywords><dates><year>2001</year><pub-dates><date>Feb 23</date></pub-dates></dates><isbn>0092-8674 (Print) 0092-8674 (Linking)</isbn><accession-num>11239409</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/11239409</url></related-urls></urls></record></Cite></EndNote>117. Based on numerous reports, skeletal muscle insulin resistance is considered as the preliminary metabolic flaw that leads to the development of this disease 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 460, 461. For instance, a marked decline in the insulin-induced Akt phosphorylation due to increased IRS-1 serine phosphorylation is reported in the offspring of T2D parents with normal glucose tolerance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 462. This implies an early molecular imprinting of muscle insulin resistance in T2D. Despite extensive investigations, the molecular faults associated with the onset of muscle insulin resistance have not been fully elucidated. Hence, identification of the key proteins that contribute to the development of muscle insulin resistance should provide important insights into the treatment of the disease.The molecular mechanisms linking obesity, ER stress, insulin action, and T2D, are widely investigated in the liver and adipose tissue 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 142. However, this complex interplay of the factors still remains poorly understood in skeletal muscle, especially in the context of ER stress. Thus, further in-depth investigations are required to delineate the molecular mechanisms regulating ER stress-induced skeletal muscle insulin resistance.Pleckstrin homology domain leucine-rich repeat protein phosphatases (PHLPPs) originally identified as Akt kinase hydrophobic motif specific phosphatases 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58 have subsequently been shown to regulate several molecules influencing the insulin signalling pathway. Abnormalities in PKB/AKT signalling in association with impaired insulin secretion resulting in insulin resistance is identified during T2D, obesity and cardiovascular disorders which brings in the relevance of PHLPPs in the metabolic paradigm. However, the functional role of PHLPP1, which inactivates Akt2, is poorly understood in the development of insulin resistance and to the best of our knowledge, the molecular circuits controlled by PHLPP1 during ER stress-induced skeletal muscle insulin resistance are yet not clear. In order to better understand the involvement of PHLPP1 in insulin resistance, we comprehensively studied the effects of PHLPP1 on the development of ER stress-induced skeletal muscle insulin resistance.2.1.Modulation of PHLPP1 expression alters glucose metabolismThe role of PHLPP1 in glucose metabolism is speculated ever since its identification. However, the underlying mechanism is poorly understood. Clinical observations by Andreozzi et al and Cozzone et al reported the enhanced expression of PHLPP1 in the adipose and skeletal muscle tissues of obese and T2D patients 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 459, 463. Over-expression of PHLPP1 in either HepG2 cells or L6 myoblasts attenuated insulin-stimulated glucose uptake via the inactivation of Akt 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ADDIN EN.CITE.DATA 459. To test the findings in our experimental setup, we altered the expression of PHLPP1, (both knockdown and forced expression approaches), and measured glucose uptake activity in L6 myoblasts using a fluorescent D-glucose analog 2-NBDG (2-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino-2-deoxy-D-glucose). Consistent with the literature, we observed that overexpression of PHLPP1 in L6 myoblasts reduced uptake of fluorescently labeled D-glucose, 2-NBDG (Figure 2.1 A). Reciprocally, ablation of PHLPP1 by shRNA in mouse myotubes (C2C12) significantly enhanced both basal as well as insulin-stimulated glucose uptake (Figure 2.1 B). Thus, the PHLPP1 expression has an inverse effect on skeletal muscle glucose uptake; however, the importance of PHLPP1 in regulating glucose homeostasis in vivo is unknown. Hence, to test the significance of the above findings in animals, we depleted PHLPP1 expression by intra-muscular injection of lentiviral driven shRNA and performed IPGTT post seven days of knockdown (Figure 2.1 C). The area under the curve (AUC) of blood glucose levels of the shPHLPP mice group was significantly lower than that of the shGFP mice group (Figure 2.1 D), indicating improved insulin sensitivity. Downregulation of PHLPP1 was confirmed by decreased expression of PHLPP1 at the protein level with ~2.5 fold enhanced phosphorylation of AKT in shPHLPP mice compared to control mice (Figure 2.1 E). Thus in concordance with literature, PHLPP1 negatively influences insulin-stimulated glucose uptake in skeletal muscle and controls glucose metabolism in vivo.Figure 2.1:PHLPP1 alters glucose sensing machinery in skeletal muscle. Basal and insulin-stimulated uptake of 2-NBDG (A) by L6 myoblasts upon SFB-PHLPP1? over-expression (insulin stimuli for 5 minutes) and (B) C2C12 myotubes upon PHLPP1 ablation (insulin stimuli for 10 minutes and 30 minutes). Statistical analysis was performed using one way ANOVA followed by Bonferrnni’s post- hoc analysis **p<0.01, ****p<0.001 vs corresponding control. (C, D) Intraperitoneal glucose tolerance test (IPGTT) (C) and (D) area under the curve (AUC) of IPGTT at the indicated times after intraperitoneal injection of glucose (n=4). Statistical analysis was performed using Student’s t-test. *p<0.05 vs shGFP. (E) Immunoblotting of indicated proteins in soleus muscle tissues of control (shGFP) and PHLPP1 knockdown (shPHLPP1) mice. Lower panel: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using Student’s t-test. **p<0.01 vs shGFP mice.2.2.PHLPP1 expression is enhanced in animals displaying insulin resistanceEarlier observations and facts from literature predict that PHLPP1 may be a negative regulator of glucose metabolism. PHLPP1 functions to impair glucose uptake in skeletal muscle and controls whole-body glucose metabolism in vivo predominantly by hindering the signalling of insulin. Thus, we sought to examine the expression of PHLPP1 in insulin resistance (IR) animal model of Diet-induced obesity (DIO) rodents e.g., mice fed with high-fat diet (HFD), rats fed with high sucrose diet (HSD) and leptin-deficient (ob/ob) mice. Firstly, we checked the expression of PHLPP1 in obese diabetic mice (Lepob/Lepob or ob/ob) which are considered as an excellent model for studying obesity and diabetes, as they have a longer lifespan and displays less severe clinical symptoms than the diabetic mice (db/db). The autosomal recessive ob/ob mice have a mutation in the leptin gene on chromosome 6 that results in a continuous sensation of hunger and thus are hyperphagic, inactive, obese, and diabetic with marked hyperglycemia ADDIN EN.CITE <EndNote><Cite><Author>Drel</Author><Year>2006</Year><RecNum>335</RecNum><DisplayText>464</DisplayText><record><rec-number>335</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>335</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Drel, V. R.</author><author>Mashtalir, N.</author><author>Ilnytska, O.</author><author>Shin, J.</author><author>Li, F.</author><author>Lyzogubov, V. V.</author><author>Obrosova, I. G.</author></authors></contributors><auth-address>Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Rd., Baton Rouge, LA 70808, USA.</auth-address><titles><title>The leptin-deficient (ob/ob) mouse: a new animal model of peripheral neuropathy of type 2 diabetes and obesity</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>3335-43</pages><volume>55</volume><number>12</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/complications/*genetics</keyword><keyword>Diabetic Neuropathies/*genetics/pathology</keyword><keyword>Disease Models, Animal</keyword><keyword>Leptin/*deficiency/genetics</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mice, Obese/*genetics</keyword><keyword>Nerve Fibers/pathology</keyword><keyword>Neural Conduction</keyword><keyword>Obesity/*genetics</keyword><keyword>Sciatic Nerve/physiopathology</keyword></keywords><dates><year>2006</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0012-1797 (Print) 0012-1797 (Linking)</isbn><accession-num>17130477</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/17130477</url></related-urls></urls><electronic-resource-num>10.2337/db06-0885</electronic-resource-num></record></Cite></EndNote>464. Consistent with the clinical observations of enhanced expression, we also found an increase in the PHLPP1 protein levels in soleus muscle of the ob/ob mice along with the ER stress markers like CHOP and BiP (Figure 2.2 A). Further, expression of PHLPP1 was also assessed in DIO rodents which also displayed well-defined characteristic features of IR such as impaired glucose tolerance, hyperinsulinemia, chronic inflammation 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ADDIN EN.CITE.DATA 465, 466 and ER stress 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 467. Consistent with the above observations, the expression of PHLPP1 was also noticed to be augmented in the soleus muscle by ~5.3 fold at the protein level in HFD mice (Figure 2.2 B) and 2 fold at the mRNA levels in HSD rats (Figure 2.2 C). Interestingly, the transcript analysis of HSD fed rats revealed an increase of PHLPP1 expression in other metabolically active insulin-sensitive tissues like liver and adipose indicating PHLPP1 might have a global role in regulating insulin sensitivity. Figure 2.2:PHLPP1 expression is elevated in insulin-resistant animals. (A, B) Immunoblotting of indicated proteins in soleus muscle tissue of ob/ob (A) and HFD mice (B). Right panel (B): Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using Student’s t-test. p<0.05, **p<0.01, ***p<0.005 vs CD. (C-E) qRT-PCR showing the abundance of PHLPP1 and ATF4 transcripts in soleus muscle (C), adipose tissue (D) and liver (E) of HSD rat. GAPDH was used as the reference gene. Statistical analysis was performed using Student’s t-test. *p<0.05,***p<0.001 vs CD. 2.3.PHLPP1 expression is enhanced under inflammation in skeletal muscleA chronic low-grade inflammation in association with dyslipidemia is responsible for the decreased peripheral insulin sensitivity in tissues such as skeletal muscle, liver, and white adipose tissue (WAT) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 174, 468. Overnutrition leads to accumulation of lipid primarily in adipocytes, resulting in enhanced expression of pro-inflammatory cytokines and activation of several signalling pathways, leading to IR either by interfering with insulin signalling and/or insulin action ADDIN EN.CITE <EndNote><Cite><Author>Chen</Author><Year>2015</Year><RecNum>339</RecNum><DisplayText>469</DisplayText><record><rec-number>339</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>339</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Chen, L.</author><author>Chen, R.</author><author>Wang, H.</author><author>Liang, F.</author></authors></contributors><auth-address>Hubei University of Chinese Medicine, Wuhan 430061, China ; Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Wuhan 430061, China. Integrated TCM and Western Medicine Department, Union Hospital, Tongji Medical College of Huazhong Science and Technology University, Wuhan 430022, China. Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Wuhan 430061, China ; Acupuncture and Moxibustion College, Hubei University of Chinese Medicine, Wuhan 430061, China.</auth-address><titles><title>Mechanisms Linking Inflammation to Insulin Resistance</title><secondary-title>Int J Endocrinol</secondary-title><alt-title>International journal of endocrinology</alt-title></titles><periodical><full-title>Int J Endocrinol</full-title><abbr-1>International journal of endocrinology</abbr-1></periodical><alt-periodical><full-title>Int J Endocrinol</full-title><abbr-1>International journal of endocrinology</abbr-1></alt-periodical><pages>508409</pages><volume>2015</volume><dates><year>2015</year></dates><isbn>1687-8337 (Print) 1687-8337 (Linking)</isbn><accession-num>26136779</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/26136779</url></related-urls></urls><custom2>4468292</custom2><electronic-resource-num>10.1155/2015/508409</electronic-resource-num></record></Cite></EndNote>469. In the earlier publication on PHLPP1 from our group, ectopic expression of PHLPP1 was observed to restrict macrophage-mediated innate immune responses, establishing the link between inflammatory responses and PHLPP1 expression ADDIN EN.CITE <EndNote><Cite><Author>Alamuru</Author><Year>2014</Year><RecNum>71</RecNum><DisplayText>371</DisplayText><record><rec-number>71</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>71</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Alamuru, N. P.</author><author>Behera, S.</author><author>Butchar, J. P.</author><author>Tridandapani, S.</author><author>Kaimal Suraj, S.</author><author>Babu, P. P.</author><author>Hasnain, S. E.</author><author>Ehtesham, N. Z.</author><author>Parsa, K. V.</author></authors></contributors><auth-address>Dr. Reddy's Institute of Life Sciences (DRILS), Hyderabad, India. Department of Biotechnology, University of Hyderabad, Hyderabad, India. Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA. Department of Biological Sciences, Indian Institute of Technology, New Delhi, India; and. National Institute of Pathology, Safdarjung Hospital, New Delhi, India. Dr. Reddy's Institute of Life Sciences (DRILS), Hyderabad, India; [email protected].</auth-address><titles><title>A novel immunomodulatory function of PHLPP1: inhibition of iNOS via attenuation of STAT1 ser727 phosphorylation in mouse macrophages</title><secondary-title>J Leukoc Biol</secondary-title><alt-title>Journal of leukocyte biology</alt-title></titles><periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></periodical><alt-periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></alt-periodical><pages>775-783</pages><volume>95</volume><number>5</number><dates><year>2014</year><pub-dates><date>May</date></pub-dates></dates><isbn>1938-3673 (Electronic) 0741-5400 (Linking)</isbn><accession-num>24443556</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24443556</url></related-urls></urls><electronic-resource-num>10.1189/jlb.0713360</electronic-resource-num></record></Cite></EndNote>371. Further, consistent with the literature and another piece of data from our group, we detected elevated level pro-inflammatory cytokines in HSD animals showing IR 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ADDIN EN.CITE.DATA 470. Thus, we wanted to test whether the expression of PHLPP1 is altered upon inflammation in skeletal muscle. For which we treated L6 myotubes with rat TNF? for different time points and observed a time-dependent increase in the expression of PHLPP1 (Figure 2.3). Interesting, similar expression time kinetics was also observed to be followed by the ER stress markers (Figure 2.3). Several pro-inflammatory cytokines are reported to trigger ER stress. For example, TNF-? activates PERK, IRE1? and ATF6 to induces ER stress in fibrosarcoma cells 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 471, while TNF-?, IL-1? and/or IL-6 induce hepatic ER stress and induce cleavage of CREBH in vivo to initiates an acute inflammatory response 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 472. Further, T-cell-derived cytokine interferon-? (IFN-?) is associated with PERK-meditated apoptosis of myelinating oligodendrocytes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 473. However, nothing is reported about inflammation induced ER stress in skeletal muscles. In this study, for the first time, we reported a time-dependent induction of ER stress markers upon TNF-? treatment. Collectively, the above data suggested that inflammation induced ER stress may be responsible for the upregulation of PHLPP1 in skeletal muscle. Hence, we sought to study if ER stress can augment the expression of PHLPP1 on itself.Figure 2.3:TNF-? enhances the expression of PHLPP1 and ER stress markers. qRT-PCR showing abundance of PHLPP1, sXBP1 and CHOP transcripts in L6 rat myotubes treated with TNF-? (10ng/ml) for the indicated time points. GAPDH was used as reference gene. 2.4.PHLPP1 expression is enhanced upon ER stress in skeletal muscle During the last decade, a considerable number of studies showed a predominant role of ER stress in the onset of the insulin resistance 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ADDIN EN.CITE.DATA 474, 475. As discussed earlier, ER stress can directly inactivate insulin signalling through several mechanisms. Serine phosphorylation of IRS-1 by IRE-1?, dephosphorylation of insulin receptor and PIP3 by ER stress-induced PTP1B and SKIP, respectively and the inactivation of Akt by TRB-3 are some of the mechanisms through which ER stress induces IR in skeletal muscle 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 475. Similar to PTP1B and SKIP 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 ADDIN EN.CITE 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ADDIN EN.CITE.DATA 342, 346, PHLPP1 also act as a negative regulator of insulin signalling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 459, however its expression upon induction of ER stress is unclear. In addition, elevated expression of PHLPP1 along with ER stress markers in IR animal models and upon pro-inflammatory cytokine treatment incited us to examine the expression of PHLPP1upon ER stress.i) PHLPP1 expression in mouse and rat myotubesTo test our hypothesis, we chemically induced ER stress using N-glycosylation inhibitor, tunicamycin and sarcoplasmic Ca2+-ATPase (SERCA) inhibitor, thapsigargin. Tunicamycin inhibits the initial step of glycoprotein biosynthesis in the ER, resulting in accumulation of unfolded glycoproteins in the ER, leading to ER stress, while Thapsigargin specifically inhibits the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) that decreases ER calcium levels as a result, inactivates the calcium-dependent ER chaperones, such as calnexin, leading to the accumulation of unfolded proteins 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 476, 477. Differentiated mouse and rat myotubes were treated with tunicamycin and thapsigargin at a concentration of 5µg/ml and 300nM, respectively and the transcript levels of PHLPP1 were analysed by qPCR. As anticipated, myotubes treated with the chemical inducer of ER stress displayed a time-dependent increase in the mRNA expression of PHLPP1 along with the ER stress marker (Figure 2.4.A, B). Consistent with the mRNA data, a time-dependent elevation in the protein levels of PHLPP1 was also detected in both mouse and rat myotubes upon treatment with tunicamycin (Figure 2.4.C, D). ii) PHLPP expression in cultured primary soleus muscle strips and in vivoFurther, we induced ER stress in cultured primary muscle strips and animals. Primary soleus muscle strips isolated from Wistar rats were cultured in the presence of tunicamycin (5µg/ml) for 3h and transcript levels of PHLPP1 were detected by qPCR. Consistent with our cellular observations, a ~ 2.4 fold increase in the expression of PHLPP1 was observed in soleus muscle strips exposed to tunicamycin. ATF4 and CHOP were used as internal controls (Figure 2.4.E). Further, to validate our finding in animals, we intraperitoneally injected mice with DMSO and/or tunicamycin for 3h. Inconsistent with our cellular and primary cell line data, we observed a ~ 2.5 fold increase in the expression of PHLPP1 in tunicamycin administered mice compared to the DMSO injected mice group, along with the upregulation of CHOP, ATF4, and sXBP1 genes (Figure 2.4. F). Thus, confirming the augmentation of PHLPP1 expression by ER stressiii) PHLPP promoter encompasses putative ER stress binding sitesTo decipher underlying mechanistic reason for the up-regulation of PHLPP1 upon ER stress, we inspected the upstream region of PHLPP1 gene and marked for the probably promoter region of PHLPP1. In our earlier publication on PHLPP1, a genomic DNA fragment encompassing the putative promoter region of PHLPP1 was cloned into a luciferase reporter vector and the promoter activity of it was confirmed (data not shown). Using that functionally active promoter sequence of PHLPP1, we analysed the potential transcription factor binding sites using Genomatix Software Suite. The analysis revealed presence of numerous putative sites of transcription factors associated with ER stress and inflammation such as ATF4, sXBP1, and NF?B. Importantly, the identified sites were also conserved across mouse, rat and human (Figure 2.G). Thus, we assume probable transcription factors binding sites in the promoter region of PHLPP1 might facilitate the integration of ER stress and/or inflammation signalling which results in augmentation of PHLPP1. Figure 2.4:PHLPP1 expression is enhanced by ER stress. (A, B) qRT-PCR showing an abundance of PHLPP1 and CHOP transcripts in mouse and rat myotubes treated with either tunicamycin (5 ?g/ml) (A) or thapsigargin (300 nM) (B) for the indicated time points. 18s and GAPDH were used as reference genes, respectively. Statistical analysis was performed using one way ANOVA followed by Dunnett’s multiple comparisons test. ap<0.05, bp<0.01, cp<0.005, dp<0.001 vs control (0 h; DMSO) (C, D) Immunoblotting using indicated antibodies in mouse and rat myotubes treated with tunicamycin for the indicated time points. (E, F) qRT-PCR for the abundance of mRNA in either freshly isolated rat soleus muscle strips (E) exposed with tunicamycin (3h) or soleus muscle samples of animals injected with tunicamycin (3h) (F). 18S was used as reference gene. Statistical analysis was performed using Student’s t-test. *p<0.05, **p<0.01, ***p<0.005 vs DMSO. (G) Genomatix Software Suite guided prediction of binding sites for ER stress-responsive transcription factors on the PHLPP1 promoter. Putative binding sites of transcription factors associated with ER stress and inflammation are highlighted in the promoter region of PHLPP1. 2.5. PHLPP1 depletion reduces the expression of ER stress markers.As the expression of PHLPP1 was augmented upon ER stress, it was appealing to understand, the impact of PHLPP1 on ER stress responses. Thus, to test the role of PHLPP1 on ER stress-inducible genes, we infected mouse myotubes with lentiviruses expressing shRNA against PHLPP1 and analysed the expression of various ER stress markers in the presence/absence of tunicamycin (5µg/ml) for 8h. shGFP lentivirus was used as the non-targeting control. Depletion of PHLPP1 marked a significant decrease in the expression of a number of tunicamycin-induced ER stress genes like BiP, CHOP, sXBP1, and TRB3, at both mRNA and protein levels (Figure 2.5A, B). Interestingly, robust reduction in the protein levels of ATF4 was noticed upon depletion of PHLPP1, while the tunicamycin-induced transcript levels of ATF4 were unaffected (Fig 2.5 B). Reciprocally to test if up-regulation of PHLPP1 can alter the expression of ER stress transducers, we overexpressed SFB-PHLPP1 or an irrelevant protein like GFP in mouse myoblasts and HEK-293T cells and analyzed the expression of ER stress markers by western blotting. Interestingly it was observed that mere over-expression of PHLPP1, but not GFP, in both mouse myoblasts (Figure 2.5 C) and HEK-293T cells (Figure 2.5 D) resulted in the up-regulation of BiP, the master sensor of UPR and activation of other ER stress-responsive proteins in a dose-dependent manner, indicating a key role for PHLPP1 in the induction of ER stress.Next, to validate our cell-based observation in vivo, we transiently ablated PHLPP1 in skeletal muscle of mice using shRNA against PHLPP1. Control animals were injected with shGFP. Post 6 days of preliminary virus administration, mice were intraperitoneally injected with DMSO and/or tunicamycin for 16h. Inconsistent with our cell-based observations, PHLPP1 knockdown mice showed a global reduction in the expression of the tunicamycin-induced ER stress-responsive genes in soleus muscle compared to the shGFP injected control animals administrated with tunicamycin (Figure 2.5 E). Thus, strengthens the key role of PHLPP1 in the induction of ER stress.Figure 2.5:PHLPP1 promotes ER stress. (A) qRT-PCR of different ER stress genes upon knockdown of PHLPP1 in C2C12 mouse myotubes treated with tunicamycin (5µg/ml) for 8h, post 48h of lentivirus infection. ?-Actin was used as the reference gene. (Inset: Immunoblotting against indicated antibodies in C2C12 confirming knockdown of PHLPP1). Statistical analysis was performed using one way ANOVA followed by Bonferroeni’s post-hoc test. **p<0.01, ***p<0.005, ****p<0.001 vs shGFP, $p<0.001 vs shGFP tc.(B) Immunoblotting of indicated proteins in PHLPP1 knockdown mouse myoblaststreated with tunicamycin (5µg/ml for 6 h). GAPDH was used as loading control.(C,D) Immunoblotting of indicated proteins in mouse myoblasts and HEK-293T ectopically expressing increasing concentrations of SFB-PHLPP1?. GFP plasmid was used as the vector control. (D) qRT-PCR showing the expression of ER stress-responsive genes upon ablation of PHLPP1 in mice. Animals were administrated with tunicamycin (5mg/kg) intraperitoneally 16h before sacrifice. 18s was used as reference gene. Statistical analysis was performed using one way ANOVA followed by Bonferroeni’s post-hoc test. **p<0.01, ***p<0.005, ****p<0.001 vs shGFP, @p<0.01, $p<0.001 vs shGFP tc. 2.6.SummaryPHLPP1 expression was noted to be upregulated in insulin-resistant animal models like ob/ob, HFD and HSD in muscle as well as other insulin-sensitive tissues like liver and adipose tissue. Mechanistically, we noticed that insulin drivers like inflammation and ER stress elevate the expression of PHLPP1 in skeletal muscle. Interestingly, depletion of PHLPP1 using shRNA showed a robust decrease in ER stress signalling both in vitro and in vivo indicating PHLPP1 as potential downstream effector as well as a regulator of ER stress. Chapter-3 AMPK? a novel substrate of PHLPP1 Key findings: PHLPP1 inactivates AMPK? by direct dephosphorylation of Thr172PHLPP1 facilitates ER stress via inhibition of AMPK activityPHLPP1 suppresses GLUT4 expression by hindering AMPK inhibited HDAC5 transcriptional repressionHaving noticed that PHLPP1 regulates both insulin sensitivity and ER stress, we searched for the potential target(s) of PHLPP1 that can regulate both ER stress and IR. PHLPP1 is known to inhibit insulin-stimulated glucose uptake, by direct dephosphorylation/inactivation of Akt 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ADDIN EN.CITE.DATA 459. However, interesting knockdown of PHLPP1 in mouse myotubes enhanced basal glucose uptake also, suggesting its potential role in insulin-independent glucose homeostasis as well (Figure 2.1B).AMP-activated protein kinase (AMPK) is a heterotrimeric complex, comprising of a catalytic subunit (?) and two regulatory subunits (? and ?) <EndNote><Cite><Author>Carling</Author><Year>2011</Year><RecNum>368</RecNum><DisplayText>[478-480]</DisplayText><record><rec-number>368</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">368</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Carling, D.</author><author>Mayer, F. V.</author><author>Sanders, M. J.</author><author>Gamblin, S. J.</author></authors></contributors><auth-address>Medical Research Council (MRC) Clinical Sciences Centre, Cellular Stress Group, Hammersmith Hospital Campus, Imperial College, London, UK. dcarling@imperial.ac.uk</auth-address><titles><title>AMP-activated protein kinase: nature&apos;s energy sensor</title><secondary-title>Nat Chem Biol</secondary-title><alt-title>Nature chemical biology</alt-title></titles><periodical><full-title>Nat Chem Biol</full-title><abbr-1>Nature chemical biology</abbr-1></periodical><alt-periodical><full-title>Nat Chem Biol</full-title><abbr-1>Nature chemical biology</abbr-1></alt-periodical><pages>512-8</pages><volume>7</volume><number>8</number><keywords><keyword>AMP-Activated Protein Kinases/genetics/*metabolism</keyword><keyword>Adenine Nucleotides/*physiology</keyword><keyword>Energy Metabolism/*physiology</keyword><keyword>Gene Expression Regulation, Enzymologic/*physiology</keyword><keyword>Signal Transduction/physiology</keyword><keyword>Species Specificity</keyword></keywords><dates><year>2011</year><pub-dates><date>Jul 18</date></pub-dates></dates><isbn>1552-4469 (Electronic)&#xD;1552-4450 (Linking)</isbn><accession-num>21769098</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21769098</url></related-urls></urls><electronic-resource-num>10.1038/nchembio.610</electronic-resource-num></record></Cite><Cite><Author>Xiao</Author><Year>2011</Year><RecNum>369</RecNum><record><rec-number>369</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">369</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Xiao, B.</author><author>Sanders, M. J.</author><author>Underwood, E.</author><author>Heath, R.</author><author>Mayer, F. V.</author><author>Carmena, D.</author><author>Jing, C.</author><author>Walker, P. A.</author><author>Eccleston, J. F.</author><author>Haire, L. F.</author><author>Saiu, P.</author><author>Howell, S. A.</author><author>Aasland, R.</author><author>Martin, S. R.</author><author>Carling, D.</author><author>Gamblin, S. J.</author></authors></contributors><auth-address>MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.</auth-address><titles><title>Structure of mammalian AMPK and its regulation by ADP</title><secondary-title>Nature</secondary-title><alt-title>Nature</alt-title></titles><periodical><full-title>Nature</full-title><abbr-1>Nature</abbr-1></periodical><alt-periodical><full-title>Nature</full-title><abbr-1>Nature</abbr-1></alt-periodical><pages>230-3</pages><volume>472</volume><number>7342</number><keywords><keyword>AMP-Activated Protein Kinases/*chemistry/genetics/*metabolism</keyword><keyword>Adenosine Diphosphate/*metabolism/*pharmacology</keyword><keyword>Adenosine Monophosphate/metabolism/pharmacology</keyword><keyword>Adenosine Triphosphate/metabolism/pharmacology</keyword><keyword>Allosteric Regulation/drug effects/genetics</keyword><keyword>Animals</keyword><keyword>Binding Sites</keyword><keyword>Crystallography, X-Ray</keyword><keyword>Enzyme Activation/drug effects/genetics</keyword><keyword>Kinetics</keyword><keyword>Magnesium/metabolism</keyword><keyword>Mammals</keyword><keyword>Models, Molecular</keyword><keyword>Phosphorylation/drug effects/genetics</keyword><keyword>Protein Binding</keyword><keyword>Protein Structure, Tertiary/drug effects/genetics</keyword><keyword>Thermodynamics</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 14</date></pub-dates></dates><isbn>1476-4687 (Electronic)&#xD;0028-0836 (Linking)</isbn><accession-num>21399626</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21399626</url></related-urls></urls><custom2>3078618</custom2><electronic-resource-num>10.1038/nature09932</electronic-resource-num></record></Cite><Cite><Author>Hardie</Author><Year>2011</Year><RecNum>370</RecNum><record><rec-number>370</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">370</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hardie, D. G.</author><author>Carling, D.</author><author>Gamblin, S. J.</author></authors></contributors><auth-address>College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK. d.g.hardie@dundee.ac.uk</auth-address><titles><title>AMP-activated protein kinase: also regulated by ADP?</title><secondary-title>Trends Biochem Sci</secondary-title><alt-title>Trends in biochemical sciences</alt-title></titles><periodical><full-title>Trends Biochem Sci</full-title><abbr-1>Trends in biochemical sciences</abbr-1></periodical><alt-periodical><full-title>Trends Biochem Sci</full-title><abbr-1>Trends in biochemical sciences</abbr-1></alt-periodical><pages>470-7</pages><volume>36</volume><number>9</number><keywords><keyword>AMP-Activated Protein Kinases/*metabolism</keyword><keyword>Adenosine Diphosphate/*metabolism</keyword><keyword>Adenosine Monophosphate/*metabolism</keyword><keyword>Adenosine Triphosphate/metabolism</keyword><keyword>Animals</keyword><keyword>Binding Sites</keyword><keyword>Electron Transport/drug effects</keyword><keyword>Energy Metabolism</keyword><keyword>Enzyme Activation</keyword><keyword>Fungal Proteins/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Glycogen/metabolism</keyword><keyword>Humans</keyword><keyword>Metformin/pharmacology</keyword><keyword>Mitochondria/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Conformation</keyword><keyword>Stilbenes/pharmacology</keyword><keyword>Transcription, Genetic</keyword><keyword>Yeasts/metabolism</keyword></keywords><dates><year>2011</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0968-0004 (Print)&#xD;0968-0004 (Linking)</isbn><accession-num>21782450</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21782450</url></related-urls></urls><electronic-resource-num>10.1016/j.tibs.2011.06.004</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Carling</Author><Year>2011</Year><RecNum>368</RecNum><DisplayText>[478-480]</DisplayText><record><rec-number>368</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">368</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Carling, D.</author><author>Mayer, F. 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J.</author><author>Underwood, E.</author><author>Heath, R.</author><author>Mayer, F. V.</author><author>Carmena, D.</author><author>Jing, C.</author><author>Walker, P. A.</author><author>Eccleston, J. F.</author><author>Haire, L. F.</author><author>Saiu, P.</author><author>Howell, S. A.</author><author>Aasland, R.</author><author>Martin, S. R.</author><author>Carling, D.</author><author>Gamblin, S. J.</author></authors></contributors><auth-address>MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.</auth-address><titles><title>Structure of mammalian AMPK and its regulation by ADP</title><secondary-title>Nature</secondary-title><alt-title>Nature</alt-title></titles><periodical><full-title>Nature</full-title><abbr-1>Nature</abbr-1></periodical><alt-periodical><full-title>Nature</full-title><abbr-1>Nature</abbr-1></alt-periodical><pages>230-3</pages><volume>472</volume><number>7342</number><keywords><keyword>AMP-Activated Protein Kinases/*chemistry/genetics/*metabolism</keyword><keyword>Adenosine Diphosphate/*metabolism/*pharmacology</keyword><keyword>Adenosine Monophosphate/metabolism/pharmacology</keyword><keyword>Adenosine Triphosphate/metabolism/pharmacology</keyword><keyword>Allosteric Regulation/drug effects/genetics</keyword><keyword>Animals</keyword><keyword>Binding Sites</keyword><keyword>Crystallography, X-Ray</keyword><keyword>Enzyme Activation/drug effects/genetics</keyword><keyword>Kinetics</keyword><keyword>Magnesium/metabolism</keyword><keyword>Mammals</keyword><keyword>Models, Molecular</keyword><keyword>Phosphorylation/drug effects/genetics</keyword><keyword>Protein Binding</keyword><keyword>Protein Structure, Tertiary/drug effects/genetics</keyword><keyword>Thermodynamics</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 14</date></pub-dates></dates><isbn>1476-4687 (Electronic)&#xD;0028-0836 (Linking)</isbn><accession-num>21399626</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21399626</url></related-urls></urls><custom2>3078618</custom2><electronic-resource-num>10.1038/nature09932</electronic-resource-num></record></Cite><Cite><Author>Hardie</Author><Year>2011</Year><RecNum>370</RecNum><record><rec-number>370</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">370</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hardie, D. G.</author><author>Carling, D.</author><author>Gamblin, S. J.</author></authors></contributors><auth-address>College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK. d.g.hardie@dundee.ac.uk</auth-address><titles><title>AMP-activated protein kinase: also regulated by ADP?</title><secondary-title>Trends Biochem Sci</secondary-title><alt-title>Trends in biochemical sciences</alt-title></titles><periodical><full-title>Trends Biochem Sci</full-title><abbr-1>Trends in biochemical sciences</abbr-1></periodical><alt-periodical><full-title>Trends Biochem Sci</full-title><abbr-1>Trends in biochemical sciences</abbr-1></alt-periodical><pages>470-7</pages><volume>36</volume><number>9</number><keywords><keyword>AMP-Activated Protein Kinases/*metabolism</keyword><keyword>Adenosine Diphosphate/*metabolism</keyword><keyword>Adenosine Monophosphate/*metabolism</keyword><keyword>Adenosine Triphosphate/metabolism</keyword><keyword>Animals</keyword><keyword>Binding Sites</keyword><keyword>Electron Transport/drug effects</keyword><keyword>Energy Metabolism</keyword><keyword>Enzyme Activation</keyword><keyword>Fungal Proteins/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Glycogen/metabolism</keyword><keyword>Humans</keyword><keyword>Metformin/pharmacology</keyword><keyword>Mitochondria/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Conformation</keyword><keyword>Stilbenes/pharmacology</keyword><keyword>Transcription, Genetic</keyword><keyword>Yeasts/metabolism</keyword></keywords><dates><year>2011</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0968-0004 (Print)&#xD;0968-0004 (Linking)</isbn><accession-num>21782450</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21782450</url></related-urls></urls><electronic-resource-num>10.1016/j.tibs.2011.06.004</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 478-480 that act as an energy sensor to regulate glucose and lipid metabolism ADDIN EN.CITE <EndNote><Cite><Author>Long</Author><Year>2006</Year><RecNum>385</RecNum><DisplayText>481</DisplayText><record><rec-number>385</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>385</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Long, Y. C.</author><author>Zierath, J. R.</author></authors></contributors><auth-address>Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.</auth-address><titles><title>AMP-activated protein kinase signaling in metabolic regulation</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>1776-83</pages><volume>116</volume><number>7</number><keywords><keyword>AMP-Activated Protein Kinases</keyword><keyword>*Energy Metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Isoenzymes/chemistry/metabolism</keyword><keyword>Multienzyme Complexes/chemistry/*metabolism</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/chemistry/*metabolism</keyword><keyword>Signal Transduction/*physiology</keyword></keywords><dates><year>2006</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0021-9738 (Print) 0021-9738 (Linking)</isbn><accession-num>16823475</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16823475</url></related-urls></urls><custom2>1483147</custom2><electronic-resource-num>10.1172/JCI29044</electronic-resource-num></record></Cite></EndNote>481. The enzyme is activated in response to changes in the intracellular AMP/ATP and ADP/ATP ratios in response to several stimuli: cellular stress, nutrient deprivation, changes in calcium concentration, or alterations in circulating levels of various hormones including leptin, cytokines, or adiponectin ADDIN EN.CITE <EndNote><Cite><Author>Viollet</Author><Year>2010</Year><RecNum>386</RecNum><DisplayText>482</DisplayText><record><rec-number>386</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>386</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Viollet, B.</author><author>Horman, S.</author><author>Leclerc, J.</author><author>Lantier, L.</author><author>Foretz, M.</author><author>Billaud, M.</author><author>Giri, S.</author><author>Andreelli, F.</author></authors></contributors><auth-address>Institut Cochin, Universite Paris Descartes, CNRS UMR 8104, Paris, France. [email protected]</auth-address><titles><title>AMPK inhibition in health and disease</title><secondary-title>Crit Rev Biochem Mol Biol</secondary-title><alt-title>Critical reviews in biochemistry and molecular biology</alt-title></titles><periodical><full-title>Crit Rev Biochem Mol Biol</full-title><abbr-1>Critical reviews in biochemistry and molecular biology</abbr-1></periodical><alt-periodical><full-title>Crit Rev Biochem Mol Biol</full-title><abbr-1>Critical reviews in biochemistry and molecular biology</abbr-1></alt-periodical><pages>276-95</pages><volume>45</volume><number>4</number><keywords><keyword>AMP-Activated Protein Kinases/chemistry/*metabolism</keyword><keyword>Animals</keyword><keyword>Down-Regulation</keyword><keyword>*Energy Metabolism</keyword><keyword>Enzyme Activation</keyword><keyword>Humans</keyword></keywords><dates><year>2010</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1549-7798 (Electronic) 1040-9238 (Linking)</isbn><accession-num>20522000</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/20522000</url></related-urls></urls><custom2>3132561</custom2><electronic-resource-num>10.3109/10409238.2010.488215</electronic-resource-num></record></Cite></EndNote>482. Several lines of evidence depict AMPK as an inter-tissue signal integrator among peripheral tissues and the hypothalamus to control whole-body energy and glucose homeostasis ADDIN EN.CITE <EndNote><Cite><Author>Long</Author><Year>2006</Year><RecNum>385</RecNum><DisplayText>481</DisplayText><record><rec-number>385</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>385</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Long, Y. C.</author><author>Zierath, J. R.</author></authors></contributors><auth-address>Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.</auth-address><titles><title>AMP-activated protein kinase signaling in metabolic regulation</title><secondary-title>J Clin Invest</secondary-title><alt-title>The Journal of clinical investigation</alt-title></titles><periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></periodical><alt-periodical><full-title>J Clin Invest</full-title><abbr-1>The Journal of clinical investigation</abbr-1></alt-periodical><pages>1776-83</pages><volume>116</volume><number>7</number><keywords><keyword>AMP-Activated Protein Kinases</keyword><keyword>*Energy Metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Humans</keyword><keyword>Isoenzymes/chemistry/metabolism</keyword><keyword>Multienzyme Complexes/chemistry/*metabolism</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/chemistry/*metabolism</keyword><keyword>Signal Transduction/*physiology</keyword></keywords><dates><year>2006</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0021-9738 (Print) 0021-9738 (Linking)</isbn><accession-num>16823475</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/16823475</url></related-urls></urls><custom2>1483147</custom2><electronic-resource-num>10.1172/JCI29044</electronic-resource-num></record></Cite></EndNote>481.AMP-activated protein kinase (AMPK) acts on glucose utilization by increasing the expression of GLUT4 and its translocation to the plasma membrane, which increases glucose uptake in skeletal muscle, independently of insulin 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 483. Furthermore, AMPK?2 knockout mice display impaired insulin-stimulated whole-body glucose utilization and skeletal muscle glycogen synthesis, although the underlying mechanisms are unknown 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 484. These studies indicate that AMPK can regulate glucose metabolism and insulin sensitivity. Mechanistically, AMPK enhances glucose utilization by increasing the expression/translocation of GLUT4, which increases glucose uptake in skeletal muscle, independently of insulin 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 483. Furthermore, AMPK?2 knockout mice display impaired insulin-stimulated whole-body glucose utilization and skeletal muscle glycogen synthesis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 484. Apart from up-regulating the glucose utilization, activation of AMPK also reduces ER stress and inflammation in skeletal muscle which are the potent drivers of insulin resistance and thus plays an important in maintaining insulin sensitivity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 338. However, the molecular events which regulate the activity of AMPK under ER stress and inflammatory signalling are not clear. 3.1.PHLPP1 regulates the activity of AMPK?The role of AMPK as a potentiator of insulin-independent glucose uptake that curbs ER stress 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 485, 486, makes it a probable downstream target of PHLPP1. Thus, PHLPP1 may (directly or indirectly) cause ER stress by inactivating AMPK. Hence, to examine whether PHLPP1 regulates ER stress in AMPK activity-dependent manner, we depleted PHLPP1 in C2C12 mouse myotubes by lentiviral shRNA and cultured them in the presence and absence of AICAR (5?-aminoimidazole-4-carboxymide-1-?-d-ribofuranoside), an agonist of AMPK 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ADDIN EN.CITE.DATA 487. Interestingly, for the first time, we observed that depletion of PHLPP1 in C2C12 mouse myotubes increased the phosphorylation of AMPK? at Thr172, which was further elevated upon AICAR treatment (Figure 3.1A). Additional, the enhanced activity of AMPK upon depletion of PHLPP1 was confirmed by elevated p-ACC levels, a substrate of AMPK; however, no change in the upstream kinase LKB1 phosphorylation status was detected (Figure 3.1A). Conversely, over-expression of PHLPP1 in mouse myoblasts and HEK-293T cells led to a dose-dependent decrease in the phosphorylation levels of AMPK? at Thr172 (Figure 3.1 B, C). Consistently, a similar dose-dependent decline in the phosphorylation levels of ACC was observed in PHLPP1 overexpressing C2C12 myoblasts, while no was p-LKB1 levels were not impacted. Above observations indicate AMPK to be a critical downstream target of PHLPP1 and encouraged us to examine whether AMPK can be a potential substrate of PHLPP1.Figure 3.1:PHLPP1 decreases AMPK? activity. (A, B) Immunoblotting analysis of PHLPP1 knockdown (A) or over-expressing (B) mouse myoblasts with the indicated antibodies. Lower panels: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using (A) one way ANOVA followed by Bonferroeni’s post-hoc test. **p<0.01, ***p<0.005 vs shGFP, @p<0.01 and #p<0.005 vs shGFP AICAR (B) one way ANOVA followed by Dunnett’s multiple comparisons test. ap<0.05 vs GFP transfected control. (C) Immunoblotting analysis of PHLPP1? over-expressing HEK-293T cells with the indicated antibodies. 3.2.PHLPP1 interacts with AMPK? To assess whether AMPK? is a substrate of PHLPP1, we first checked for the interaction between PHLPP1 and AMPK?. The IP-MS/MS data obtained from ComPASS (a free and open-source software that analysis high-throughput proteomics data obtained from mass spectrometry search algorithm ADDIN EN.CITE <EndNote><Cite><Author>Wenger</Author><Year>2011</Year><RecNum>681</RecNum><DisplayText>488</DisplayText><record><rec-number>681</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>681</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Wenger, C. D.</author><author>Phanstiel, D. H.</author><author>Lee, M. V.</author><author>Bailey, D. J.</author><author>Coon, J. J.</author></authors></contributors><auth-address>Department of Chemistry, University of Wisconsin, Madison, WI, USA.</auth-address><titles><title>COMPASS: a suite of pre- and post-search proteomics software tools for OMSSA</title><secondary-title>Proteomics</secondary-title><alt-title>Proteomics</alt-title></titles><periodical><full-title>Proteomics</full-title><abbr-1>Proteomics</abbr-1></periodical><alt-periodical><full-title>Proteomics</full-title><abbr-1>Proteomics</abbr-1></alt-periodical><pages>1064-74</pages><volume>11</volume><number>6</number><keywords><keyword>*Algorithms</keyword><keyword>Chromatography, Liquid</keyword><keyword>Computational Biology</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Databases, Protein/statistics & numerical data</keyword><keyword>Proteins/isolation & purification/standards</keyword><keyword>Proteomics/methods/standards/*statistics & numerical data</keyword><keyword>Reference Standards</keyword><keyword>Saccharomyces cerevisiae Proteins/isolation & purification</keyword><keyword>*Software</keyword><keyword>Tandem Mass Spectrometry/statistics & numerical data</keyword></keywords><dates><year>2011</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1615-9861 (Electronic) 1615-9853 (Linking)</isbn><accession-num>21298793</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21298793</url></related-urls></urls><custom2>3049964</custom2><electronic-resource-num>10.1002/pmic.201000616</electronic-resource-num></record></Cite></EndNote>488) ., PHLPP1 was predicted to interact with the ? subunit of AMPK, a heterotrimeric protein complex formed by ?, ?, and ? subunits (Figure 3.2 A). Thus, to assess whether PHLPP1 interacts with AMPK?, we precipitated SFB-PHLPP1? from HEK-293T cells using streptavidin beads and detected co-precipitation of AMPK? along with PHLPP1 upon western blotting (Figure 3.2 B). Next, to assess the interaction endogenously, we immunoprecipitated PHLPP1 from C2C12 mouse myotubes and detected an enrichment of endogenous AMPK? along with reported partners of PHLPP like Akt & p70S6K but not with AMPK upstream kinase LKB1 or p38 (Figure 3.2 C). Interestingly, the endogenous association between PHLPP1 phosphatase and AMPK? was enhanced upon treatment of tunicamycin in C2C12 cells for 4 hours. However, the association of AMPK with other known phosphatases like PP2A catalytic domain (PP2Ac) was not affected 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 489 (Figure 3.2 D). Although PP2C is known to dephosphorylate AMPK 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 490 it didn’t show interaction with AMPK in mouse myotubes either basally or upon induction of ER stress. In parallel, we observed a decrease in the interaction of AMPK with its upstream kinase (LKB1) or its substrates (ACC, HDAC5) due to tunicamycin treatment (Figure 3.2 D). To test the relevance of PHLPP1 as the in vivo phosphatase of AMPK, we did reverse immunoprecipitation of AMPK? from soleus muscle tissue of control diet and HFD fed mice. Consistent with cell culture data, we observed an enhanced association of AMPK? with PHLPP1in the soleus muscle of HFD mice, while it’s binding with its substrates (ACC and HDAC5) and upstream kinase (LKB1) was reduced (Figure 3.2 E). Consistent with myotube observations, the interaction of PP2Ac with AMPK? was not influenced by HFD feeding. However, the expression levels of PP2C? were increased due to HFD feeding, but its interaction with AMPK? was not detectable in either control diet or HFD fed mice (Figure 3.2 E). Further, it was witnessed that the complex formation between PHLPP1 and AMPK? but not Akt, was disrupted upon activation of AMPK by AICAR or a more selective AMPK activator A769662 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 491, 492 (Figure 3.2 F) as AMPK upon activation undergoes conformational change that hinders the accesses of its phosphatases. The above observations suggest that PHLPP1 as the unidentified phosphatase of AMPK?, thus we next sought to validate whether PHLPP1 can directly dephosphorylate AMPK? or not.Figure 3.2:Interaction of PHLPP1 with AMPK? is enhanced upon ER stress. (A) CompPASS analysis of various interacting partners of PHLPP1. Z score determines the number of standard deviations away from mean; however it does not take into account whether a protein is found in a duplicate run or not. TAP% indicates the percentage of all IP-MS/MS experiments in which the interaction was detected. (B) Immunoblotting analysis of SFB-PHLPP1? precipitates from HEK-293T cells with the indicated antibodies. (C) Immunoblotting analysis of endogenous PHLPP1 immunoprecipitates from myoblasts with the indicated antibodies. Akt and p70S6K were used as positive control. Bottom panel: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using Student’s t-test. ***p<0.001 vs mock. (D) Western blot analysis of endogenous AMPK? immunoprecipitates from tunicamycin-treated myoblasts with the indicated antibodies. Right panel: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using Student’s t-test. *p<0.05,**p<0.01 vs mock. ns, non-significant. (E) Western blot analysis of endogenous AMPK? immunoprecipitates from soleus muscle of control diet (CD) or high fat diet fed (HFD) mice with the indicated antibodies. Bottom panel: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using Student’s t-test. *p<0.05,**p<0.01 vs CD. ns, non-significant. (F) Immunoblotting showing interaction between PHLPP1, AMPK and Akt upon treatment with tunicamycin (5?g/ml for 8h) and AMPK activators AICAR (500?M for 30 min) and A-769662 (50µM for 45 min). Bottom panel: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using one way ANOVA followed by Tukey’s Multiple Comparison Test . ***p<0.005, ****p<0.001 vs cells transfected with SFB-PHLPP1? (WT), $p<0.001 vs tunicamycin treated SFB-PHLPP1? (WT) transfected ns, non-significant. 3.3.In vitro dephosphorylation of AMPK? by PHLPP1Although the most commonly expressed isoform of AMPK in cells is AMPK1 isoform (with ?1, ?1, and ?1 subunits), yet it has been demonstrated that AMPK isoforms comprising of ?1?2?2 is predominant in the heart and ?2?2?1 is the major isoform seen in skeletal muscle 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 493. When cellular AMP:ATP ratio increases the four Cystathionine beta-synthase (CBS) domains on the ? subunit create two binding sites for AMP, called Bateman domains, which upon binding of AMP brings about a conformational change in the ? subunit that exposes the phosphorylation site Thr172 in the catalytic domain located on ? subunit 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ADDIN EN.CITE 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Three upstream kinases LKB1 ADDIN EN.CITE <EndNote><Cite><Author>Woods</Author><Year>2003</Year><RecNum>345</RecNum><DisplayText>495</DisplayText><record><rec-number>345</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>345</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Woods, A.</author><author>Johnstone, S. R.</author><author>Dickerson, K.</author><author>Leiper, F. C.</author><author>Fryer, L. G.</author><author>Neumann, D.</author><author>Schlattner, U.</author><author>Wallimann, T.</author><author>Carlson, M.</author><author>Carling, D.</author></authors></contributors><auth-address>Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.</auth-address><titles><title>LKB1 is the upstream kinase in the AMP-activated protein kinase cascade</title><secondary-title>Curr Biol</secondary-title><alt-title>Current biology : CB</alt-title></titles><periodical><full-title>Curr Biol</full-title><abbr-1>Current biology : CB</abbr-1></periodical><alt-periodical><full-title>Curr Biol</full-title><abbr-1>Current biology : CB</abbr-1></alt-periodical><pages>2004-8</pages><volume>13</volume><number>22</number><keywords><keyword>AMP-Activated Protein Kinases</keyword><keyword>Animals</keyword><keyword>Blotting, Western</keyword><keyword>Chromatography, Ion Exchange</keyword><keyword>Enzyme Activation</keyword><keyword>Liver/metabolism</keyword><keyword>Multienzyme Complexes/*metabolism</keyword><keyword>Precipitin Tests</keyword><keyword>Protein-Serine-Threonine Kinases/*metabolism</keyword><keyword>Rats</keyword></keywords><dates><year>2003</year><pub-dates><date>Nov 11</date></pub-dates></dates><isbn>0960-9822 (Print) 0960-9822 (Linking)</isbn><accession-num>14614828</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/14614828</url></related-urls></urls></record></Cite></EndNote>495, CAMKK2 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ADDIN EN.CITE.DATA 497 are known to phosphorylate AMPK at the Thr172 to activate it. Based on the comparative sequence analysis of the putative consensus dephosphorylation site of PHLPP ADDIN EN.CITE <EndNote><Cite><Author>Li</Author><Year>2013</Year><RecNum>88</RecNum><DisplayText>498</DisplayText><record><rec-number>88</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>88</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Li, X.</author><author>Wilmanns, M.</author><author>Thornton, J.</author><author>Kohn, M.</author></authors></contributors><auth-address>Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.</auth-address><titles><title>Elucidating human phosphatase-substrate networks</title><secondary-title>Sci Signal</secondary-title><alt-title>Science signaling</alt-title></titles><periodical><full-title>Sci Signal</full-title><abbr-1>Science signaling</abbr-1></periodical><alt-periodical><full-title>Sci Signal</full-title><abbr-1>Science signaling</abbr-1></alt-periodical><pages>rs10</pages><volume>6</volume><number>275</number><keywords><keyword>Databases, Protein</keyword><keyword>Humans</keyword><keyword>*Models, Biological</keyword><keyword>Phosphoric Monoester Hydrolases/*metabolism</keyword><keyword>Phosphorylation/physiology</keyword><keyword>Sequence Analysis, Protein</keyword><keyword>*Systems Biology</keyword></keywords><dates><year>2013</year><pub-dates><date>May 14</date></pub-dates></dates><isbn>1937-9145 (Electronic) 1945-0877 (Linking)</isbn><accession-num>23674824</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23674824</url></related-urls></urls><electronic-resource-num>10.1126/scisignal.2003203</electronic-resource-num></record></Cite></EndNote>498, we predicted both AMPK?1 and AMPK?2 activating phosphorylation site of Thr172 as a potential target sites for PHLPP1 (Figure 3.3 A). Thus, to confirm AMPK? as a direct substrate of PHLPP1, we performed time kinetic dephosphorylation assay of PHLPP1. PP2C? was used as the positive control. The assay revealed that HEK-293T cell purified SFB tagged PHLPP1? phosphatase was able to significantly dephosphorylate recombinant active AMPK? as early as 15 min post incubation. However, robust dephosphorylation of AMPK? by PHLPP1 comparable to PP2C? was apparent after 90 min of incubation, with nearly complete dephosphorylation at 180 min (Figure 3.3 B). On the other hand, consistent with literature 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 490, incubation of AMPK complex with HEK-293T cell purified SFB-PP2C? resulted in robust dephosphorylation of AMPK? as early as 15 min (Figure 3.3 B). SFB-PH-LRR domain (truncated PHLPP1? mutant consisting of only PH and LRR domains) was used as the negative control. Collectively the aforesaid observations confirm AMPK? as a novel bonafide substrate of PHLPP1. Figure 3.3:AMPK is a novel target of PHLPP1. (A) Sequence alignment of AMPK? with the putative PHLPP1 substrate sequence. PHLPP1 putative sequence was derived from only six de-phosphorylation sites originating from 3 proteins Akt, PKC and Mst1. However, there seems to be exceptions in the allowed amino acids of the putative sequence which are shown in the bottom panel. (B) In vitro phosphatase assay of HEK 293T cell purified PHLPP1 and PP2C? using recombinant AMPK as the substrate. SFB-PH-LRR was used as the control. Bottom panel: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using Student’s t-test. *p<0.05, **p<0.01 vs SFB-PH-LRR control.3.4.PHLPP1 facilitates ER stress by inhibition of AMPK activityAfter confirming AMPK as a substrate of PHLPP1, we next explored the role of the PHLPP1/AMPK axis in ER stress response. A reduced activation of AMPK is noted in many genetic rodent models with a metabolic syndrome, including ob/ob mice (leptin-deficient), fa/fa rats (leptin receptor-deficient) and the male ZDF rat (leptin receptor-deficient with a mutation in the insulin promoter); along with enhanced ER stress markers in the insulin-sensitive organs 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 486, 494. More importantly, ER stress-mediated AMPK inactivation has not yet been compared in skeletal muscle of normal subjects and obese patients. Cell-based studies indicate that the activation of AMPK attenuates ER stress, thus making AMPK a therapeutic target for the treatment of ER stress-mediated metabolic diseases ADDIN EN.CITE <EndNote><Cite><Author>Steinberg</Author><Year>2009</Year><RecNum>373</RecNum><DisplayText>499</DisplayText><record><rec-number>373</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>373</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Steinberg, G. R.</author><author>Kemp, B. E.</author></authors></contributors><auth-address>Protein Chemistry and Metabolism, St. Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Victoria, Australia. [email protected]</auth-address><titles><title>AMPK in Health and Disease</title><secondary-title>Physiol Rev</secondary-title><alt-title>Physiological reviews</alt-title></titles><periodical><full-title>Physiol Rev</full-title><abbr-1>Physiological reviews</abbr-1></periodical><alt-periodical><full-title>Physiol Rev</full-title><abbr-1>Physiological reviews</abbr-1></alt-periodical><pages>1025-78</pages><volume>89</volume><number>3</number><keywords><keyword>AMP-Activated Protein Kinases/*physiology</keyword><keyword>Animals</keyword><keyword>Cardiovascular Diseases/physiopathology</keyword><keyword>Energy Metabolism/*physiology</keyword><keyword>Humans</keyword><keyword>Metabolic Syndrome/physiopathology</keyword><keyword>Neoplasms/physiopathology</keyword><keyword>Neurodegenerative Diseases/physiopathology</keyword><keyword>Obesity/physiopathology</keyword></keywords><dates><year>2009</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0031-9333 (Print) 0031-9333 (Linking)</isbn><accession-num>19584320</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/19584320</url></related-urls></urls><electronic-resource-num>10.1152/physrev.00011.2008</electronic-resource-num></record></Cite></EndNote>499. AICAR, an allosteric activator of AMPK, is taken up by the adenosine transporters of cells as an adenosine analog and subsequently phosphorylated by adenosine kinase to generate the AMP-mimetic, AICAR monophosphate (ZMP), which similarly to cellular AMP, binds to site 3 on the AMPK? subunit and activates the AMPK complex 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 500. AICAR improves the endothelium-dependent relaxation in isolated mouse aortae 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 501 and protects cardiomyocytes from hypoxia injury through attenuation of ER stress 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 339. Further, treatment of HFD-fed mice with AICAR prevented nutrient-induced hepatic lipid accumulation by inhibiting mTORC1 and ER stress 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ADDIN EN.CITE.DATA 308. Metformin, an indirect AMPK activator, is widely studied in alleviating ER stress. Metformin, an anti-hyperglycemic drug, acts as an indirect activator of AMPK by inhibiting complex I of the mitochondrial respiratory chain, leading to an increased AMP: ATP ratio ADDIN EN.CITE <EndNote><Cite><Author>Owen</Author><Year>2000</Year><RecNum>350</RecNum><DisplayText>502</DisplayText><record><rec-number>350</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>350</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Owen, M. R.</author><author>Doran, E.</author><author>Halestrap, A. P.</author></authors></contributors><auth-address>Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.</auth-address><titles><title>Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain</title><secondary-title>Biochem J</secondary-title><alt-title>The Biochemical journal</alt-title></titles><periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></periodical><alt-periodical><full-title>Biochem J</full-title><abbr-1>The Biochemical journal</abbr-1></alt-periodical><pages>607-14</pages><volume>348 Pt 3</volume><keywords><keyword>Animals</keyword><keyword>Electron Transport/drug effects</keyword><keyword>Electron Transport Complex I</keyword><keyword>Gluconeogenesis/drug effects</keyword><keyword>Hypoglycemic Agents/*pharmacology</keyword><keyword>Liver/drug effects/metabolism</keyword><keyword>Male</keyword><keyword>Metformin/*pharmacology</keyword><keyword>Mitochondria/*drug effects/enzymology</keyword><keyword>NADH, NADPH Oxidoreductases/*antagonists & inhibitors</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Signal Transduction</keyword><keyword>Submitochondrial Particles/enzymology</keyword><keyword>Tumor Cells, Cultured</keyword></keywords><dates><year>2000</year><pub-dates><date>Jun 15</date></pub-dates></dates><isbn>0264-6021 (Print) 0264-6021 (Linking)</isbn><accession-num>10839993</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/10839993</url></related-urls></urls><custom2>1221104</custom2></record></Cite></EndNote>502. Metformin ameliorates hepatic insulin resistance under hyperlipidemic conditions 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ADDIN EN.CITE.DATA 503 and protects rat insulinoma cells from palmitate-induced phosphorylation of eIF2?, JNK, and IRS-1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 504. In addition, treatment of tubular HK-2 cells with metformin constrains renal fibrosis via suppressing ER stress, which is reversed upon siRNA mediated knockdown of AMPK 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 505. Furthermore, metformin ameliorates ER stress-mediated high-fat diet-induced endothelial dysfunction in diabetic obese mice by AMPK-induced PPAR? activation 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ADDIN EN.CITE.DATA 506 and corrected the impaired contractile function in the mammalian heart related to mTOR activation and ER stress 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 507, indicating its therapeutic role in cardiovascular disease. Thus mechanistically, activation of AMPK suppresses ER stress-responsive genes like CHOP and TRB3, which regulates the glucose sensing pathways 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 475, 486. Conversely, under pathophysiological conditions such as chronic inflammation and obesity, intracellular ER stress is elevated which leads to reduced AMPK activity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 57, 486, however, the molecular insight regulating the AMPK activity under ER stress is still obscure. Thus, based on our previous observations, we speculated that ER stress-induced PHLPP1 may regulate AMPK driven UPR response. Hence, to investigate the role of PHLPP1 on AMPK modulated ER stress responses; firstly, we assessed the role of PHLPP1 in ER stress-mediated inhibition of AMPK. As expected, treatment of C2C12 cells with tunicamycin reduced the phosphorylation of AMPK? and ACC. Ablation of PHLPP1 not only elevated basal phosphorylation levels of AMPK and ACC but also relieved tunicamycin-induced suppression of AMPK and ACC phosphorylation (Figure 4.4 A). Then after, we overexpressed PHLPP1? in mouse myoblasts and then incubated the cells with AMPK activators AICAR or A769662 and assessed the ER-responsive signals. Unlike AICAR, A-769662 shows high specificity toward AMPK. The ability of A-769662 to directly activate AMPK in cell-free assays as well as under cellular conditions makes it unique among currently known cell-permeable activators. Moreover, the strong synergic in AMPK activation by AMP and A-769662 has been reported both in vitro and in vivo, indicating that A-769662 and AMP have different binding sites on the AMPK complex and thus different mechanisms of activation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 491. Consistent with our previous observations, ectopic expression of PHLPP1 augmented ER-responsive genes expression, treatment of PHLPP1 over-expressing cells with AICAR or A769662 increased the phosphorylation of AMPK and dampened the phosphorylation of eIF2?, PERK and total protein levels of CHOP and ATF4 (Figure 4.4 B). Thus, PHLPP1 acts as the phosphatase that inactivates AMPK to facilitate ER stress. Figure 3.4:PHLPP1 facilitates ER stress by inhibiting AMPK. A) Western blotting analysis of tunicamycin-treated control or PHLPP1 knockdown myoblasts with the indicated antibodies. Right panel: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using one way ANOVA followed by Bonferroeni’s post-hoc test. **p<0.01, vs shGFP, @p<0.01 vs shGFP tc. (B) Immunoblotting of indicated proteins in SFB-PHLPP1? over-expressing C2C12 mouse myoblasts treated with AMPK activators AICAR (500µM for 30 mins) or A769662 (50µM for 45 min). GFP expressing plasmid was used as the transfection control. Right panels: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using one way ANOVA followed by Bonferroeni’s post-hoc test. *p<0.05, **p<0.01, ***p<0.005 vs GFP, &p<0.05, @p<0.01, $p<0.001 vs SFB-PHLPP1?. 3.5.PHLPP1 suppresses GLUT4 expressionHaving demonstrated that PHLPP1 regulates AMPK driven ER stress and thus impairs glucose uptake in skeletal muscle, we next address the impact of PHLPP1 on GLUT4 expression, the key glucose transporter of both insulin-dependent and insulin-independent glucose uptake. In response to insulin stimuli or exercise, GLUT4 is translocated to the cell surface, where it facilitates the uptake of glucose into the insulin-responsive tissues ADDIN EN.CITE <EndNote><Cite><Author>Lacombe</Author><Year>2014</Year><RecNum>391</RecNum><DisplayText>508</DisplayText><record><rec-number>391</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>391</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lacombe, V. A.</author></authors></contributors><auth-address>Department of Physiology Sciences, Center of Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.</auth-address><titles><title>Expression and regulation of facilitative glucose transporters in equine insulin-sensitive tissue: from physiology to pathology</title><secondary-title>ISRN Vet Sci</secondary-title><alt-title>ISRN veterinary science</alt-title></titles><periodical><full-title>ISRN Vet Sci</full-title><abbr-1>ISRN veterinary science</abbr-1></periodical><alt-periodical><full-title>ISRN Vet Sci</full-title><abbr-1>ISRN veterinary science</abbr-1></alt-periodical><pages>409547</pages><volume>2014</volume><dates><year>2014</year></dates><isbn>2090-4452 (Print) 2090-4452 (Linking)</isbn><accession-num>24977043</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24977043</url></related-urls></urls><custom2>4060548</custom2><electronic-resource-num>10.1155/2014/409547</electronic-resource-num></record></Cite></EndNote>508. Mechanistically, both AMPK and Akt (secondary messenger of exercise and insulin, respectively), phosphorylates and inhibits AS160, which facilitates GLUT4 translocation to the cellular surface 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 509, 510. Apart from translocation, AMPK also regulates HDAC5 driven GLUT4 transcription. AMPK is reported to phosphorylate histone deacetylase 5 (HDAC5), the transcriptional repressor of GLUT4 gene, at Ser-259 and Ser-498. AICAR treatment results in HDAC5 phosphorylation, association with 14-3-3 isoforms, and H3 acetylation, altogether resulting in a reduced HDAC5 association with the GLUT4 promoter concomitant with increases in GLUT4 gene expression in human primary myotubes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 511. Conversely, treatment of mouse myotubes with chemical chaperones like 4-PBA enhance GLUT4 transcript and protein levels 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 512. Thus, we speculated that PHLPP1 might have an inhibitory effect on GLUT4 expression. As anticipated, we observed a dramatic reduction in the protein levels of GLUT4, but not GLUT1, in a dose-dependent manner upon forced expression of PHLPP1? in mouse myoblasts (Figure 3.5 A). In parallel, we observed a dose-dependent increase in HDAC5; the AMPK regulated transcriptional repressor of the GLUT4 gene (Figure 3.5 A). Transcriptional repression of GLUT4 is observed upon activation of ER stress in 3T3L1 cells contributing to adiposity insulin resistance. ER stress inhibits the activity and expression of C/EBP?, an activator of GLUT4 expression by inducing the expression of CHOP10, an inhibitor of C/EBP? activation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 513. Consistent with previous reports, GLUT4 but not GLUT1 levels were dramatically reduced in tunicamycin-treated cells with concomitant up-regulation of HDAC5 protein levels (Figure 3.5 B). The fact that the expression of PHLPP1 is upregulated upon ER stress and it suppressed the expression of GLUT4, promoted us to examine whether PHLPP1 can induce ER stress-mediated GLUT4 suppression in myotubes. Indeed ablation of PHLPP1 nullified tunicamycin-induced HDAC5 expression and relieved tunicamycin-mediated GLUT4 suppression (Figure 3.5 B). Further, shRNA mediated PHLPP1 knockdown in mice led to ~4.1 fold induction of GLUT4 protein in the soleus muscle (Figure 3.5 C). Thus, ER stress inhibits GLUT4 expression by upregulation of PHLPP1 which inhibits AMPK promoting HDAC5 facilitated transcriptional repression of GLUT4.Figure 3.5:PHLPP1 suppresses GLUT4 expression. (A) Western blot analysis of SFB-PHLPP1? over-expressing myoblasts with the indicated antibodies. GFP plasmid was used as the transfection control. Bottom panels: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using one way ANOVA followed by Dunnett’s multiple comparisons test. ap<0.05, bp<0.01, cp<0.005, dp<0.001 vs GFP control. ns, non-significant. (B) Immunoblotting analysis of tunicamycin-treated PHLPP1 knockdown myoblasts with the indicated antibodies. Bottom panel: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using one way ANOVA followed by Bonferroeni’s post-hoc test. *p<0.05, ***p<0.005 vs shGFP, @p<0.01, #p<0.005 vs shGFP tc. ns, non-significant. (C) Immunoblotting analysis of soleus muscle of PHLPP1 knockdown mice with the indicated antibodies. M1 to M8 represent different mice. Bottom panels: Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using Student’s t-test. *p<0.05 vs shGFP. 3.6.SummaryIn this chapter, utilizing biochemical assay and cell-based techniques; we established that PHLPP1 dephosphorylates AMPK Thr172 located in its activation loop; thereby PHLPP1 hinders AMPK activity and restricts downstream signalling including the suppression of ER stress and expression of GLUT4. Further, we noticed that the interaction between PHLPP1 and AMPK is dynamic and is modulated by ER stress and AMPK activators. Thus, we conclude PHLPP1 by direct inhibition of AMPK triggers ER stress.Chapter-4PHLPP1 is phosphorylated by ERK1/2 upon ER stress85897615049500Key findings: ERK1/2 phosphorylates PHLPP1? at Ser932 both in vitro and in vivoER stress augments ERK1/2 mediated phosphorylation of PHLPP1The influence of PHLPP1 on vital cell signalling circuits like Akt, PKC, MAPK 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 514, 515 and AMPK (this study) is progressively gaining importance. Thus, being a crucial player in maintaining cellular homeostasis, the expressional level of PHLPP1, at both mRNA and protein, is tightly regulated at all stages of gene regulation, starting from DNA methylation, to transcription and post-transcription, to translation and post-translational modifications. Epigenetic modulations like DNA hypermethylation in chronic lymphocytic leukemia (CLL) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 384, hypomethylation in osteoarthritis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 385 and inhibition of HDAC3 in osteoblasts 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 386 influences the PHLPP1 gene expression. Regulation of PHLPP1 expression at the transcriptional level though less understood has been reported to be regulated via TGF-? in T-cells 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 387. Also, our group noted a steady decrease in the levels of expression of both PHLPP1 isoforms upon exposure to bacterial endotoxin ADDIN EN.CITE <EndNote><Cite><Author>Alamuru</Author><Year>2014</Year><RecNum>186</RecNum><DisplayText>516</DisplayText><record><rec-number>186</rec-number><foreign-keys><key app=”EN” db-id=”0rz0tr0xhs5rv9e9exox09f2safwpdse2fpe”>186</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Alamuru, N. P.</author><author>Behera, S.</author><author>Butchar, J. P.</author><author>Tridandapani, S.</author><author>Kaimal Suraj, S.</author><author>Babu, P. P.</author><author>Hasnain, S. E.</author><author>Ehtesham, N. Z.</author><author>Parsa, K. V.</author></authors></contributors><auth-address>*Dr. Reddy's Institute of Life Sciences (DRILS), Hyderabad, India;</auth-address><titles><title>A novel immunomodulatory function of PHLPP1: inhibition of iNOS via attenuation of STAT1 ser727 phosphorylation in mouse macrophages</title><secondary-title>J Leukoc Biol</secondary-title><alt-title>Journal of leukocyte biology</alt-title></titles><periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></periodical><alt-periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></alt-periodical><dates><year>2014</year><pub-dates><date>Jan 17</date></pub-dates></dates><isbn>1938-3673 (Electronic) 0741-5400 (Linking)</isbn><accession-num>24443556</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24443556</url></related-urls></urls><electronic-resource-num>10.1189/jlb.0713360</electronic-resource-num></record></Cite></EndNote>516. In addition, several oncogenic miRNAs are associated with regulation of both PHLPP1 and PHLPP2 expression. The expression of PHLPP isozymes at the translational level is controlled by mTOR-dependent protein translation. Inhibition of mTOR activity reduces PHLPP1 expression via S6K and 4E-BP1 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 366, 419. In addition, PHLPP1 protein stability is controlled by calpains, ?-TrCP 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 369, 420 and several deubiquitinases like USP1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 424, USP12 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ADDIN EN.CITE.DATA 425, and 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 426.Yet, the cellular mechanism regulating its catalytic activity is poorly understood. Intriguingly, several reports have shown that the functional activities of proteins are modulated via post-translational phosphorylation events. However, a sole report by Zhang et al. shows that during insulin signalling PHLPP1 is Tyr phosphorylated which was associated with its enhanced phosphatase activity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 428. Interestingly, in the pursuit of the mechanism regulating the PHLPP1 catalytic activity, we identified a large number of predicted kinase sites on PHLPP1. But the effect of such post-translational phospho-modification of the protein is yet to be revealed. Hence deciphering mechanisms underlying the activity, localization, and stability of PHLPP will provide novel insights into the biological functions of this new player in cellular studies.4.1.In silico analysis of PHLPP1 phosphorylation sitesTo decipher the post-translational mechanisms controlling the catalytic activity of PHLPP1, we performed in silico analysis using an algorithm called ScanSite. ScanSite searches for motifs within proteins that are likely to be phosphorylated by specific kinases or bind to domains such as SH2 domains or PDZ domains ADDIN EN.CITE <EndNote><Cite><Author>Obenauer</Author><Year>2003</Year><RecNum>90</RecNum><DisplayText>517</DisplayText><record><rec-number>90</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>90</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Obenauer, J. C.</author><author>Cantley, L. C.</author><author>Yaffe, M. B.</author></authors></contributors><auth-address>Center for Cancer Research, E18-580, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.</auth-address><titles><title>Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs</title><secondary-title>Nucleic Acids Res</secondary-title><alt-title>Nucleic acids research</alt-title></titles><periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></periodical><alt-periodical><full-title>Nucleic Acids Res</full-title><abbr-1>Nucleic acids research</abbr-1></alt-periodical><pages>3635-41</pages><volume>31</volume><number>13</number><keywords><keyword>Algorithms</keyword><keyword>*Amino Acid Motifs</keyword><keyword>Binding Sites</keyword><keyword>Databases, Protein</keyword><keyword>Internet</keyword><keyword>Phosphorylation</keyword><keyword>Protein Structure, Tertiary</keyword><keyword>Proteins/chemistry/metabolism</keyword><keyword>Proteome/*chemistry/metabolism</keyword><keyword>Sequence Analysis, Protein/*methods</keyword><keyword>Signal Transduction</keyword><keyword>*Software</keyword></keywords><dates><year>2003</year><pub-dates><date>Jul 01</date></pub-dates></dates><isbn>1362-4962 (Electronic) 0305-1048 (Linking)</isbn><accession-num>12824383</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/12824383</url></related-urls></urls><custom2>168990</custom2></record></Cite></EndNote>517. Thus, using this algorithm we noticed numerous kinase sites on PHLPP1 which may potentially alter its functionality (Table 1). Out of the several predicted kinases, ERK1/2 was preferentially selected as the potential candidate to phosphorylate PHLPP1. It was previously reported that PHLPP1 constrains MAPK/ERK pathway through the inhibition of Ras and Raf activity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 349, 372; moreover, a recent report by Hwang et al shows an inhibitory crosstalk between AMPK and ERK1/2 signalling that mediates ER stress-induced insulin resistance in skeletal muscle 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ADDIN EN.CITE.DATA 337. Further, in an earlier report from our group, we demonstrated that TNF-? mediated ERK2 dependent phosphorylation of a co-activator binding protein PIMT regulates skeletal muscle glucose metabolism via controlling GLUT4 expression <EndNote><Cite><Author>Kain</Author><Year>2015</Year><RecNum>9</RecNum><DisplayText>[470, 518]</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611488">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kain, V.</author><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Seshadri, S.</author><author>Prajapati, B.</author><author>Jena, P. K.</author><author>Teja Meda, C. L.</author><author>Subramanian, M.</author><author>Kaimal Suraj, S.</author><author>Kumar, S. T.</author><author>Prakash Babu, P.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Parsa, K. V.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr. Reddy&apos;s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.&#xD;Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>Co-activator binding protein PIMT mediates TNF-alpha induced insulin resistance in skeletal muscle via the transcriptional down-regulation of MEF2A and GLUT4</title><secondary-title>Sci Rep</secondary-title></titles><periodical><full-title>Sci Rep</full-title></periodical><pages>15197</pages><volume>5</volume><edition>2015/10/16</edition><keywords><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Cells, Cultured</keyword><keyword>Down-Regulation/drug effects</keyword><keyword>Glucose Transporter Type 4/genetics/*metabolism</keyword><keyword>HEK293 Cells</keyword><keyword>Histone Deacetylases/genetics/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin Resistance</keyword><keyword>MEF2 Transcription Factors/genetics/metabolism</keyword><keyword>Male</keyword><keyword>Mitogen-Activated Protein Kinase 1/metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 3/metabolism</keyword><keyword>Myoblasts, Skeletal/cytology/metabolism</keyword><keyword>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Transcription Factors/genetics/metabolism</keyword><keyword>Transcription, Genetic/*drug effects</keyword><keyword>Tumor Necrosis Factor-alpha/blood/*pharmacology</keyword></keywords><dates><year>2015</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>2045-2322 (Electronic)&#xD;2045-2322 (Linking)</isbn><accession-num>26468734</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26468734</url></related-urls></urls><custom2>PMC4606566</custom2><electronic-resource-num>10.1038/srep15197</electronic-resource-num></record></Cite><Cite><Author>Kapadia</Author><Year>2013</Year><RecNum>8</RecNum><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611456">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Parsa, K. V.</author><author>Kain, V.</author><author>Behera, S.</author><author>Suraj, S. K.</author><author>Babu, P. P.</author><author>Kar, A.</author><author>Panda, S.</author><author>Zhu, Y. J.</author><author>Jia, Y.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr Reddy&apos;s Institute of Life Sciences, An Associate Institute of University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Life Sciences, Devi Ahilya University, Indore, Madhya Pradesh, India.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>ERK2-mediated phosphorylation of transcriptional coactivator binding protein PIMT/NCoA6IP at Ser298 augments hepatic gluconeogenesis</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e83787</pages><volume>8</volume><number>12</number><edition>2013/12/21</edition><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Female</keyword><keyword>Gene Expression Regulation/drug effects</keyword><keyword>Gluconeogenesis/drug effects/*physiology</keyword><keyword>Glucose/biosynthesis</keyword><keyword>Hepatocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Liver/*metabolism</keyword><keyword>MAP Kinase Signaling System/drug effects</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mitogen-Activated Protein Kinase 1/*metabolism</keyword><keyword>Models, Biological</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>Protein Binding</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/genetics</keyword><keyword>Rats</keyword><keyword>Substrate Specificity</keyword><keyword>Thyroid Hormones/pharmacology</keyword><keyword>Transcription, Genetic</keyword><keyword>Transcriptional Activation</keyword></keywords><dates><year>2013</year></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>24358311</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/24358311</url></related-urls></urls><custom2>PMC3866170</custom2><electronic-resource-num>10.1371/journal.pone.0083787</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Kain</Author><Year>2015</Year><RecNum>9</RecNum><DisplayText>[470, 518]</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611488">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kain, V.</author><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Seshadri, S.</author><author>Prajapati, B.</author><author>Jena, P. K.</author><author>Teja Meda, C. L.</author><author>Subramanian, M.</author><author>Kaimal Suraj, S.</author><author>Kumar, S. T.</author><author>Prakash Babu, P.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Parsa, K. V.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr. Reddy&apos;s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.&#xD;Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>Co-activator binding protein PIMT mediates TNF-alpha induced insulin resistance in skeletal muscle via the transcriptional down-regulation of MEF2A and GLUT4</title><secondary-title>Sci Rep</secondary-title></titles><periodical><full-title>Sci Rep</full-title></periodical><pages>15197</pages><volume>5</volume><edition>2015/10/16</edition><keywords><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Cells, Cultured</keyword><keyword>Down-Regulation/drug effects</keyword><keyword>Glucose Transporter Type 4/genetics/*metabolism</keyword><keyword>HEK293 Cells</keyword><keyword>Histone Deacetylases/genetics/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin Resistance</keyword><keyword>MEF2 Transcription Factors/genetics/metabolism</keyword><keyword>Male</keyword><keyword>Mitogen-Activated Protein Kinase 1/metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 3/metabolism</keyword><keyword>Myoblasts, Skeletal/cytology/metabolism</keyword><keyword>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Transcription Factors/genetics/metabolism</keyword><keyword>Transcription, Genetic/*drug effects</keyword><keyword>Tumor Necrosis Factor-alpha/blood/*pharmacology</keyword></keywords><dates><year>2015</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>2045-2322 (Electronic)&#xD;2045-2322 (Linking)</isbn><accession-num>26468734</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26468734</url></related-urls></urls><custom2>PMC4606566</custom2><electronic-resource-num>10.1038/srep15197</electronic-resource-num></record></Cite><Cite><Author>Kapadia</Author><Year>2013</Year><RecNum>8</RecNum><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611456">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Parsa, K. V.</author><author>Kain, V.</author><author>Behera, S.</author><author>Suraj, S. K.</author><author>Babu, P. P.</author><author>Kar, A.</author><author>Panda, S.</author><author>Zhu, Y. J.</author><author>Jia, Y.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr Reddy&apos;s Institute of Life Sciences, An Associate Institute of University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Life Sciences, Devi Ahilya University, Indore, Madhya Pradesh, India.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>ERK2-mediated phosphorylation of transcriptional coactivator binding protein PIMT/NCoA6IP at Ser298 augments hepatic gluconeogenesis</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e83787</pages><volume>8</volume><number>12</number><edition>2013/12/21</edition><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Female</keyword><keyword>Gene Expression Regulation/drug effects</keyword><keyword>Gluconeogenesis/drug effects/*physiology</keyword><keyword>Glucose/biosynthesis</keyword><keyword>Hepatocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Liver/*metabolism</keyword><keyword>MAP Kinase Signaling System/drug effects</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mitogen-Activated Protein Kinase 1/*metabolism</keyword><keyword>Models, Biological</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>Protein Binding</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/genetics</keyword><keyword>Rats</keyword><keyword>Substrate Specificity</keyword><keyword>Thyroid Hormones/pharmacology</keyword><keyword>Transcription, Genetic</keyword><keyword>Transcriptional Activation</keyword></keywords><dates><year>2013</year></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>24358311</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/24358311</url></related-urls></urls><custom2>PMC3866170</custom2><electronic-resource-num>10.1371/journal.pone.0083787</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 470, 518. To further strengthen our prediction, we performed in silico analysis using ScanSite and found the consensus ERK1/2 kinase site (PXS/TP) of PHLPP, to be conserved across different species, with a highly reliable score of less than 0.2% (Table 2). Additional analysis using NetPhos (phosphorylation site prediction algorithm) 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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CbG9tPC9BdXRob3I+PFllYXI+MTk5OTwvWWVhcj48UmVjTnVtPjkxPC9SZWNOdW0+PERpc3BsYXlUZXh0Pls1MTldPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjkxPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0icGR0c2F2ZWQ3cHB3cjBlMHMycXZ6MnpmMHd4cngyeGQwYWF2Ij45MTwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+QmxvbSwgTi48L2F1dGhvcj48YXV0aG9yPkdhbW1lbHRvZnQsIFMuPC9hdXRob3I+PGF1dGhvcj5CcnVuYWssIFMuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBvZiBCaW90ZWNobm9sb2d5LCBUaGUgVGVjaG5pY2FsIFVuaXZlcnNpdHkgb2YgRGVubWFyaywgTHluZ2J5LCBESy0yODAwLCBEZW5tYXJrLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPlNlcXVlbmNlIGFuZCBzdHJ1Y3R1cmUtYmFzZWQgcHJlZGljdGlvbiBvZiBldWthcnlvdGljIHByb3RlaW4gcGhvc3Bob3J5bGF0aW9uIHNpdGVzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkogTW9sIEJpb2w8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkpvdXJuYWwgb2YgbW9sZWN1bGFyIGJpb2xvZ3k8L2FsdC10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIE1vbCBCaW9sPC9mdWxsLXRpdGxlPjxhYmJyLTE+Sm91cm5hbCBvZiBtb2xlY3VsYXIgYmlvbG9neTwvYWJici0xPjwvcGVyaW9kaWNhbD48YWx0LXBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SiBNb2wgQmlvbDwvZnVsbC10aXRsZT48YWJici0xPkpvdXJuYWwgb2YgbW9sZWN1bGFyIGJpb2xvZ3k8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz4xMzUxLTYyPC9wYWdlcz48dm9sdW1lPjI5NDwvdm9sdW1lPjxudW1iZXI+NTwvbnVtYmVyPjxrZXl3b3Jkcz48a2V5d29yZD5BbWlubyBBY2lkIE1vdGlmczwva2V5d29yZD48a2V5d29yZD5BbWlubyBBY2lkIFNlcXVlbmNlPC9rZXl3b3JkPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtleXdvcmQ+QmluZGluZyBTaXRlczwva2V5d29yZD48a2V5d29yZD4qQ29uc2Vuc3VzIFNlcXVlbmNlPC9rZXl3b3JkPjxrZXl3b3JkPkV1a2FyeW90aWMgQ2VsbHMvKmNoZW1pc3RyeTwva2V5d29yZD48a2V5d29yZD5HbHljb3N5bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPk1vZGVscywgTW9sZWN1bGFyPC9rZXl3b3JkPjxrZXl3b3JkPk5ldXJhbCBOZXR3b3JrcyAoQ29tcHV0ZXIpPC9rZXl3b3JkPjxrZXl3b3JkPk51Y2xlYXIgUHJvdGVpbnMvY2hlbWlzdHJ5L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+UGhvc3Bob3Byb3RlaW5zLypjaGVtaXN0cnkvKm1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+UGhvc3Bob3J5bGF0aW9uPC9rZXl3b3JkPjxrZXl3b3JkPlBoeWxvZ2VueTwva2V5d29yZD48a2V5d29yZD5Qcm90ZWluIFN0cnVjdHVyZSwgVGVydGlhcnk8L2tleXdvcmQ+PGtleXdvcmQ+UmVwcm9kdWNpYmlsaXR5IG9mIFJlc3VsdHM8L2tleXdvcmQ+PGtleXdvcmQ+U2Vuc2l0aXZpdHkgYW5kIFNwZWNpZmljaXR5PC9rZXl3b3JkPjxrZXl3b3JkPlNlcmluZS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlN1YnN0cmF0ZSBTcGVjaWZpY2l0eTwva2V5d29yZD48a2V5d29yZD5UaHJlb25pbmUvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5UcmFucy1BY3RpdmF0b3JzL2NoZW1pc3RyeS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlR5cm9zaW5lL21ldGFib2xpc208L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MTk5OTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkRlYyAxNzwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjAwMjItMjgzNiAoUHJpbnQpJiN4RDswMDIyLTI4MzYgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjEwNjAwMzkwPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzEwNjAwMzkwPC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDA2L2ptYmkuMTk5OS4zMzEwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn== ADDIN EN.CITE.DATA 519, indicated that ERK1/2 target site on PHLPP1, among different species, has a higher probability for accepting the incoming phosphate group.It is reported that ERK1/2 for its efficient activity needs transient enzyme-substrate interactions and also requires some additional docking interactions. One such domain is D-domain on the substrate which is involved in electrostatic interactions between positively charged residues of D-domain and negatively charged Asp in the common docking (CD) site of the enzyme. Hydrophobic residues in both D and CD domain also play a role in stabilizing the interactions <EndNote><Cite><Author>Vomastek</Author><Year>2008</Year><RecNum>44</RecNum><DisplayText>[520-523]</DisplayText><record><rec-number>44</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">44</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vomastek, T.</author><author>Iwanicki, M. P.</author><author>Burack, W. R.</author><author>Tiwari, D.</author><author>Kumar, D.</author><author>Parsons, J. T.</author><author>Weber, M. J.</author><author>Nandicoori, V. K.</author></authors></contributors><auth-address>National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.</auth-address><titles><title>Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>6954-66</pages><volume>28</volume><number>22</number><keywords><keyword>Animals</keyword><keyword>COS Cells</keyword><keyword>Cercopithecus aethiops</keyword><keyword>Humans</keyword><keyword>MAP Kinase Kinase 1/genetics/metabolism</keyword><keyword>MAP Kinase Signaling System/physiology</keyword><keyword>Mitogen-Activated Protein Kinase 1/chemistry/genetics/*metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 14/genetics/metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 8/genetics/metabolism</keyword><keyword>Nuclear Pore/*metabolism</keyword><keyword>Nuclear Pore Complex Proteins/chemistry/genetics/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Structure, Tertiary</keyword><keyword>Proto-Oncogene Proteins/genetics/*metabolism</keyword><keyword>Recombinant Fusion Proteins/genetics/metabolism</keyword><keyword>Serine/metabolism</keyword><keyword>Threonine/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1098-5549 (Electronic)&#xD;0270-7306 (Linking)</isbn><accession-num>18794356</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18794356</url></related-urls></urls><custom2>2573295</custom2><electronic-resource-num>10.1128/MCB.00925-08</electronic-resource-num></record></Cite><Cite><Author>Lee</Author><Year>2011</Year><RecNum>45</RecNum><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">45</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lee, S.</author><author>Warthaka, M.</author><author>Yan, C.</author><author>Kaoud, T. S.</author><author>Ren, P.</author><author>Dalby, K. N.</author></authors></contributors><auth-address>Division of Medicinal Chemistry, University of Texas at Austin, Texas 78712, United States.</auth-address><titles><title>Examining docking interactions on ERK2 with modular peptide substrates</title><secondary-title>Biochemistry</secondary-title><alt-title>Biochemistry</alt-title></titles><periodical><full-title>Biochemistry</full-title><abbr-1>Biochemistry</abbr-1></periodical><alt-periodical><full-title>Biochemistry</full-title><abbr-1>Biochemistry</abbr-1></alt-periodical><pages>9500-10</pages><volume>50</volume><number>44</number><keywords><keyword>Allosteric Regulation</keyword><keyword>Amino Acid Sequence</keyword><keyword>Catalytic Domain</keyword><keyword>Hydrophobic and Hydrophilic Interactions</keyword><keyword>Mitogen-Activated Protein Kinase 1/*chemistry/metabolism</keyword><keyword>Molecular Sequence Data</keyword><keyword>Peptides/*chemistry/metabolism</keyword><keyword>Protein Binding</keyword><keyword>Protein Transport</keyword><keyword>Substrate Specificity</keyword></keywords><dates><year>2011</year><pub-dates><date>Nov 08</date></pub-dates></dates><isbn>1520-4995 (Electronic)&#xD;0006-2960 (Linking)</isbn><accession-num>21955038</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21955038</url></related-urls></urls><custom2>3422614</custom2><electronic-resource-num>10.1021/bi201103b</electronic-resource-num></record></Cite><Cite><Author>Gonzalez</Author><Year>1991</Year><RecNum>46</RecNum><record><rec-number>46</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">46</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gonzalez, F. A.</author><author>Raden, D. L.</author><author>Davis, R. J.</author></authors></contributors><auth-address>Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605.</auth-address><titles><title>Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>22159-63</pages><volume>266</volume><number>33</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Cell Line</keyword><keyword>Humans</keyword><keyword>Kinetics</keyword><keyword>Mitogen-Activated Protein Kinase 1</keyword><keyword>Mitogen-Activated Protein Kinase 3</keyword><keyword>*Mitogen-Activated Protein Kinases</keyword><keyword>Molecular Sequence Data</keyword><keyword>Peptides/chemical synthesis/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Kinases/isolation &amp; purification/*metabolism</keyword><keyword>Receptor, Epidermal Growth Factor/metabolism</keyword><keyword>Substrate Specificity</keyword></keywords><dates><year>1991</year><pub-dates><date>Nov 25</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>1939237</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/1939237</url></related-urls></urls></record></Cite><Cite><Author>Lee</Author><Year>2011</Year><RecNum>47</RecNum><record><rec-number>47</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">47</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lee, S.</author><author>Warthaka, M.</author><author>Yan, C.</author><author>Kaoud, T. S.</author><author>Piserchio, A.</author><author>Ghose, R.</author><author>Ren, P.</author><author>Dalby, K. N.</author></authors></contributors><auth-address>Division of Medicinal Chemistry, University of Texas at Austin, Austin, Texas, United States of America.</auth-address><titles><title>A model of a MAPK*substrate complex in an active conformation: a computational and experimental approach</title><secondary-title>PLoS One</secondary-title><alt-title>PloS one</alt-title></titles><periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></periodical><alt-periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></alt-periodical><pages>e18594</pages><volume>6</volume><number>4</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Biocatalysis</keyword><keyword>Catalytic Domain</keyword><keyword>Computational Biology/*methods</keyword><keyword>Ligands</keyword><keyword>Mice</keyword><keyword>Mitogen-Activated Protein Kinase 1/antagonists &amp;</keyword><keyword>inhibitors/*chemistry/*metabolism</keyword><keyword>*Models, Molecular</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutation/genetics</keyword><keyword>Peptides/chemistry</keyword><keyword>Phosphorylation</keyword><keyword>Protein Binding</keyword><keyword>Protein Conformation</keyword><keyword>Proto-Oncogene Protein c-ets-1/*chemistry/genetics/*metabolism</keyword><keyword>Substrate Specificity</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 11</date></pub-dates></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>21494553</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21494553</url></related-urls></urls><custom2>3073974</custom2><electronic-resource-num>10.1371/journal.pone.0018594</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Vomastek</Author><Year>2008</Year><RecNum>44</RecNum><DisplayText>[520-523]</DisplayText><record><rec-number>44</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">44</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vomastek, T.</author><author>Iwanicki, M. P.</author><author>Burack, W. R.</author><author>Tiwari, D.</author><author>Kumar, D.</author><author>Parsons, J. T.</author><author>Weber, M. J.</author><author>Nandicoori, V. K.</author></authors></contributors><auth-address>National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India.</auth-address><titles><title>Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction</title><secondary-title>Mol Cell Biol</secondary-title><alt-title>Molecular and cellular biology</alt-title></titles><periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></periodical><alt-periodical><full-title>Mol Cell Biol</full-title><abbr-1>Molecular and cellular biology</abbr-1></alt-periodical><pages>6954-66</pages><volume>28</volume><number>22</number><keywords><keyword>Animals</keyword><keyword>COS Cells</keyword><keyword>Cercopithecus aethiops</keyword><keyword>Humans</keyword><keyword>MAP Kinase Kinase 1/genetics/metabolism</keyword><keyword>MAP Kinase Signaling System/physiology</keyword><keyword>Mitogen-Activated Protein Kinase 1/chemistry/genetics/*metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 14/genetics/metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 8/genetics/metabolism</keyword><keyword>Nuclear Pore/*metabolism</keyword><keyword>Nuclear Pore Complex Proteins/chemistry/genetics/*metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein Structure, Tertiary</keyword><keyword>Proto-Oncogene Proteins/genetics/*metabolism</keyword><keyword>Recombinant Fusion Proteins/genetics/metabolism</keyword><keyword>Serine/metabolism</keyword><keyword>Threonine/metabolism</keyword></keywords><dates><year>2008</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1098-5549 (Electronic)&#xD;0270-7306 (Linking)</isbn><accession-num>18794356</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/18794356</url></related-urls></urls><custom2>2573295</custom2><electronic-resource-num>10.1128/MCB.00925-08</electronic-resource-num></record></Cite><Cite><Author>Lee</Author><Year>2011</Year><RecNum>45</RecNum><record><rec-number>45</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">45</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lee, S.</author><author>Warthaka, M.</author><author>Yan, C.</author><author>Kaoud, T. S.</author><author>Ren, P.</author><author>Dalby, K. N.</author></authors></contributors><auth-address>Division of Medicinal Chemistry, University of Texas at Austin, Texas 78712, United States.</auth-address><titles><title>Examining docking interactions on ERK2 with modular peptide substrates</title><secondary-title>Biochemistry</secondary-title><alt-title>Biochemistry</alt-title></titles><periodical><full-title>Biochemistry</full-title><abbr-1>Biochemistry</abbr-1></periodical><alt-periodical><full-title>Biochemistry</full-title><abbr-1>Biochemistry</abbr-1></alt-periodical><pages>9500-10</pages><volume>50</volume><number>44</number><keywords><keyword>Allosteric Regulation</keyword><keyword>Amino Acid Sequence</keyword><keyword>Catalytic Domain</keyword><keyword>Hydrophobic and Hydrophilic Interactions</keyword><keyword>Mitogen-Activated Protein Kinase 1/*chemistry/metabolism</keyword><keyword>Molecular Sequence Data</keyword><keyword>Peptides/*chemistry/metabolism</keyword><keyword>Protein Binding</keyword><keyword>Protein Transport</keyword><keyword>Substrate Specificity</keyword></keywords><dates><year>2011</year><pub-dates><date>Nov 08</date></pub-dates></dates><isbn>1520-4995 (Electronic)&#xD;0006-2960 (Linking)</isbn><accession-num>21955038</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21955038</url></related-urls></urls><custom2>3422614</custom2><electronic-resource-num>10.1021/bi201103b</electronic-resource-num></record></Cite><Cite><Author>Gonzalez</Author><Year>1991</Year><RecNum>46</RecNum><record><rec-number>46</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">46</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gonzalez, F. 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S.</author><author>Piserchio, A.</author><author>Ghose, R.</author><author>Ren, P.</author><author>Dalby, K. N.</author></authors></contributors><auth-address>Division of Medicinal Chemistry, University of Texas at Austin, Austin, Texas, United States of America.</auth-address><titles><title>A model of a MAPK*substrate complex in an active conformation: a computational and experimental approach</title><secondary-title>PLoS One</secondary-title><alt-title>PloS one</alt-title></titles><periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></periodical><alt-periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></alt-periodical><pages>e18594</pages><volume>6</volume><number>4</number><keywords><keyword>Amino Acid Sequence</keyword><keyword>Animals</keyword><keyword>Biocatalysis</keyword><keyword>Catalytic Domain</keyword><keyword>Computational Biology/*methods</keyword><keyword>Ligands</keyword><keyword>Mice</keyword><keyword>Mitogen-Activated Protein Kinase 1/antagonists &amp;</keyword><keyword>inhibitors/*chemistry/*metabolism</keyword><keyword>*Models, Molecular</keyword><keyword>Molecular Sequence Data</keyword><keyword>Mutation/genetics</keyword><keyword>Peptides/chemistry</keyword><keyword>Phosphorylation</keyword><keyword>Protein Binding</keyword><keyword>Protein Conformation</keyword><keyword>Proto-Oncogene Protein c-ets-1/*chemistry/genetics/*metabolism</keyword><keyword>Substrate Specificity</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr 11</date></pub-dates></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>21494553</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/21494553</url></related-urls></urls><custom2>3073974</custom2><electronic-resource-num>10.1371/journal.pone.0018594</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 520-523. To check the presence of such docking site on PHLPP1, we performed computational analysis and found that PHLPP1 contains two such ERK-D domains and 2 DEF motifs (Table 3, Figure 4.1). From the above computational analysis and literature surveys, we envisage that ERK1/2 may modulate the activity of PHLPP1 via phosphorylation, as an integral feedback control loop.Table 1: Predicted kinase sites of PHLPP1? with their respective percentile scores (Scansite prediction). Scores in Scansite start at 0.000 if the sequence optimally matches the given motif, and the scores increase for sequences as they diverge from the optimal match. Sites with a score less than 0.2% are considered as good hits. Table 2: Conserved putative ERK1 phosphorylation site (PPSP) of PHLPP1? in various species.Table 3: Predicted ERK D-domains of PHLPP1? across different species according to Scansite motif analysis.Figure 4.1:Schematic representation of PHLPP1? protein with consensus Erk1/2 phosphoacceptor sites and ERK interactions docking (D motif: DEF motif) along with the conserved regulatory domains. 4.2. PHLPP1 is a substrate of ERK1/2 To validate PHLPP1 as a substrate of ERK1/2, we performed in vitro kinase assay using GST-PP2C* (the catalytic domain of PHLPP1 with essential ERK1/2 sites). Upon incubation of GST-PP2C* with rERK1 or HEK-293T purified GST-ERK2 protein, we observed the incorporation of ?-32P into GST-PP2C* (Figure 4.2 A). To rule out the inhibitory effect of other domains on ERK1/2-mediated PHLPP1 phosphorylation, streptavidin affinity purified full-length PHLPP1? protein was incubated with active rERK1 protein. An enhanced phosphorylation of PHLPP1? was examined anti-MPM2 antibody (ERK substrate antibody that recognizes p-S/TP motif), upon incubation with rERK1 kinase (Figure 4.2 B).To examine ERK-mediated PHLPP1 phosphorylation in intact cells, we transfected HEK-293T cells with a combination of plasmids as indicated in the Figure 4.2 C. SFB PHLPP1? protein precipitate from protein matched lysates using streptavidin agarose beads, followed by western blotting analysis using specific antibodies. Consistent with above observations, phospho-signals of PHLPP1? detected by MPM-2 antibody was enhanced upon activation of ERK1/2 by co-transfection with Raf-BXB (constitutively active mutant of Raf 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 524). In addition, over-expression of Raf-BXB also increased the protein levels of ectopically expressed PHLPP1?. To test the impact of Raf-BXB/MEK/ERK axis on PHLPP1? expression, we blocked MEK1/ERK1 pathway using pharmacological inhibitor U0126 and noticed drastic reduction in the expression of SFB-PHLPP1? in HEK-293T cells (Figure 4.2 D), while no change in expression of endogenous PHLPP1 was observed in altering the endogenous PHLPP1 levels in either C2C12 myoblasts or THP-1 monocytic cells (Figure 4.2 E, F), indicating a cell type-specific effect. Figure 4.2:PHLPP1 is phosphorylated by ERK1/2. (A) Autoradiography showing in vitro kinase assay of GST-PP2C* with rERK1 and GST-ERK2 protein. (B) Immunoblotting showing in vitro phosphorylation of full length SFB-PHLPP1? wild protein by rERK1. Phospho signals were detected with the anti-MPM2 antibody. Right side panel: Signals were quantified using ImageJ graphics software. (C) Immunoblotting with MPM2 antibody showing phosphorylation of PHLPP1? wild in intact cells upon ERK1/2 activation via Raf-BXB. The same blot was stripped and re-probed with anti-Flag or anti-PHLPP1. Right side panel: Signals were quantified using ImageJ graphics software. (D-F) Western blot analysis of SFB-PHLPP1? overexpressing HEK-293T cells and endogenous PHLPP1 in (D) C2C12 myoblasts (E) and human monocyte THP-1 monocytic cells (F) exposed to UO126 or SB203580 with the indicated antibodies. UO126: MEK1/2 inhibitor; SB203580: p38 inhibitor.4.3.Confirmation of Ser932 as the site of ERK1/2 phosphorylation To confirm the predicted Ser932 site of PHLPP1? (Ser1444 PHLPP1?) as the phospho-acceptor site for ERK1/2, we performed in vitro kinase assay using the GST-PP2C* (WT), Ser932Ala, Ser932Asp mutants. Mutation of Ser932 to either Ala or Asp remarkably reduced the ERK1/2-dependent phosphorylation of GST-PP2C* (Figure 4.3 A). Thus, to confirm the phosphorylation of PHLPP1? by ERK1/2 specifically in intact cells, we developed a custom antibody that could specifically detect phospho Ser932 PHLPP1. The phospho-specific antibody was raised in rabbit and its specificity for pSer932 residue was confirmed by ELISA (Table 4). To further validate the authenticate of Ser932 phospho-site specific antibody, we performed western blotting analysis of in vitro kinase assay using rERK1and GST-ERK2 with affinity purified SFB-PHLPP1? WT and Ser932Ala mutant proteins. Concurrent with our auto-radiographic data, mutation of the ERK1/2 target site i.e; Ser 932 to Ala abolished ERK1/2 mediated phosphorylation of PHLPP1? (Figure 4.3 B, C). Figure 4.3: PHLPP1 is phosphorylated at Ser932 residue by ERK1/2 in vitro. (A) Autoradiography showing in vitro kinase assay of GST-PP2C* wild and Ser932 mutants with rERK1. CS: Coomassie blue staining. (B) Immunoblotting with MPM-2 antibody showing phosphorylation of PHLPP1? wild at Ser932 in intact cells upon ERK1/2 activation via Raf-BXB. SFB-PHLPP1?Ser932 Ala mutant was used as negative control.(C,D) Immunoblotting showing in vitro phosphorylation of full-length SFB-PHLPP1? wild protein by rERK1 (C) and GST-ERK2 (D). SFB-PHLPP1?Ser932 Ala mutant was used to confirm site specificity.Table 4: ELISA results for the pre-immune serum and phospho-specific antibody after the 3rd immunization. Starting dilution: 1:1,000 is equivalent to 1 µg/ml. The titer is the highest dilution with S/B (Signal/Blank) >=2.1.NC is negative control (Pre-immune serum).4.4. PHLPP1 is phosphorylated by ERK1/2 in intact cells To validate ERK1/2 mediated phosphorylation of PHLPP1 in intact cells; we first ablated PHLPP1 using human shRNA in HEK-293T cells and analysed for the off-target effects of the site-specific phospho-antibody in cells. PHLPP1? was observed to be minimally phosphorylated at Ser932 under basal conditions, while the phospho-signals were lost upon knockdown of PHLPP1, endorsing the specificity of the antibody (Figure 4.4 A). Then to demonstrate ERK1/2 mediated PHLPP1 phosphomodication, we transfected HEK-293T cells with SFB-PHLPP1? WT and Ser932 mutants along with Raf-BXB followed by western blotting using site-specific phospho-antibody. Co-transfection of PHLPP1? with Raf-BXB significantly enhanced Ser932 phosphorylation in wild-type PHLPP1?, mutations of Ser932 to Ala or Asp abolished the Raf-BXB dependent phosphorylation of PHLPP1? (Figure 4.4 B). Similarly, co-transfection of PHLPP1? with ERK1 or ERK2 also augmented phosphorylation levels of Ser932, which were further improved upon co-transfection of Raf-BXB (Figure 4.4 C). Additional confocal analysis of HEK-293T transiently expressing SFB-PHLPP1? in the presence or absence of Raf-BXB with site-specific phospho-antibody, showed a minimally basal phosphorylation of PHLPP1? at Ser932 which was robustly enhanced upon co-transfection with Raf-BXB, confirming Ser932 as the site of ERK1/2 phosphorylation in cells (Figure 4.4 D). PHLPP1?, an alternatively spliced variant of PHLPP1?, also encompasses ERK1/2 phosphoacceptor site (Ser1444), whereas isoforms of PHLPP1, PHLPP2 lacks it (Figure 4.4 E). To examine the specificity of ERK1/2 phosphorylations towards PHLPP1, we analysed the phosphorylation status of PHLPP isozymes in the presence or absence of Raf-BXB in HEK-293T cells using site-specific Ser932 phospho- antibody. Both the spliced variants of PHLPP1 were observed to be phosphorylated at Ser932 upon activation of MAPK/ERK pathway, whereas no modification in the phosphorylation state of PHLPP2 was detected (Figure 4.4 E). Thus, we concluded that ERK1/2 phosphorylates PHLPP1 at the novel Ser932 site. Having observed that ERK1/2 phosphorylates PHLPP1, we then examined the impact of PHLPP1 on ERK1/2 activation as a part of feedback control. Over-expression of PHLPP1? dose-dependently elevated phosphorylation levels of ERK1/2 and JNK1/2 in C2C12 myoblasts but suppressed phosphorylation of another MAPK, p38 (Figure 4.4 F). Reciprocally, knockdown of PHLPP1 in myoblasts attenuated the phosphorylation of ERK1/2 and JNK1/2 and enhanced the phospho signals of p38 (Figure 4.4 G).Figure 4.4:PHLPP1 is a substrate of ERK1/2 in intact cells. (A) Confocal analysis of control or PHLPP1 knockdown HEK-293T cells using pSer932 PHLPP1 antibody (red) detected by Alexa Fluor 647 tagged anti-rabbit secondary antibody (B, C) Immunoblotting showing phosphorylation of PHLPP1? wild at Ser932 in intact cells upon ERK1/2 activation via Raf-BXB (B) or ectopic expression of ERK1 and ERK2 plasmids (C). (D) Confocal analysis of phospho-PHLPP1 in PHLPP1 transfected HEK-293T cells co-expressing RafBXB using pSer932-PHLPP1 antibody (red) detected by Alexa Fluor 647 tagged anti-rabbit secondary antibody. Nuclei were stained by DAPI (blue). (E) Immunoblotting of PHLPP isoforms by indicated antibodies. Top panel: Multiple sequence alignment of the ERK1/2 target region of PHLPP isoforms. (F, G) Immunoblot analysis of SFB-PHLPP1? over-expressing (F) or AICAR treated PHLPP1 knockdown C2C12 cells (G) with the indicated antibodies. GFP plasmid was used as the transfection control (F). 4.5.ER stress induces ERK1/2 mediated PHLPP1 phosphorylation To understand the impact of this phosphorylation upon the cellular functionality of PHLPP1, it was essential to identify the physiological/pathological circumstances which impact the phosphorylation. ER-stress is known to inhibit insulin-stimulated glucose uptake while exposure to UO126 promotes glucose uptake both insulin dependent and independent probably through activation of AMPK in rat myotubes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 337, 470. Considering the facts that PHLPP1 facilitates ER stress through the inhibition of AMPK and that PHLPP1 is phosphorylated by ERK1/2, we examined whether ER stress can induce ERK1/2 mediated PHLPP1 phosphorylation at the Ser932 site. As per our prediction, Ser932 phosphorylation of PHLPP1? was elevated upon exposure to tunicamycin in both concentration and time-dependent manner in HEK-293T cells (Figure 4.5 A, B).Next, to examine the ER stress-induced ERK1/2-mediated PHLPP1 phosphorylation in muscle, we treated L6 myoblasts with increasing concentrations of tunicamycin for 24 hours and observed a dose-dependent increase in PHLPP1 phosphorylation (Figure 4.5 C). Similarly, enhanced phosphorylation of PHLPP1 at Ser932 was detected by confocal analysis in tunicamycin-treated L6 myoblasts (Figure 4.5 D). Furthermore, Ser932 phosphorylation of PHLPP1? was readily observed in ex vivo cultured primary rat soleus muscle strips exposed to tunicamycin (Figure 4.5 E). To validate the ERK1/2 mediated PHLPP1 phosphorylation in vivo, we examined phosphorylation of PHLPP1 at Ser932 in insulin-resistant animals associated with elevated ER stress with chronic inflammation. As anticipated, the phosphorylation of PHLPP1? at Ser932 residue was enhanced in the soleus muscle of HFD mice (Figures 4.5 F). Thus, we conclude that PHLPP1 is phosphorylated at Ser932 residue during ER stress. Figure 4.5:Phosphorylation of PHLPP1 at Ser932 is enhanced upon ER stress. (A, B) Immunoblot showing dose-dependent effects (A) and time kinetics (B) of tunicamycin (tc) treatment on Ser932 phosphorylation of PHLPP1? in HEK-293T cells transfected with SFB-PHLPP1?. (C) Immunoblotting analysis of L6 myoblasts exposed to different concentrations of tunicamycin with the indicated antibodies. (D) Confocal microscopy analysis of L6 myoblasts exposed to tunicamycin (5?g/ml) using pSer932-PHLPP1 antibody. (E) Western blot analysis of freshly isolated rat soleus muscle strips exposed to different concentrations of tunicamycin with the indicated antibodies.(F, G) Immunoblot analysis of the soleus muscle of HFD fed animals animals with the indicated antibodies. Bottom panel (F): Densitometric analysis of western blot signals. Data are represented as mean+SEM. Statistical analysis was performed using Student’s t-test. **p<0.01 vs control diet (CD). 4.6.Summary In this chapter, using bioinformatics tool, we predicted that PHLPP1 may be phospho-modified by ERK1/2 at Ser932, a well-conserved phosphorylation site of ERK1/2 on PHLPP1. Presence of ERK docking site further strengthened our prediction which was ascertained using radioactive in vitro kinase assay as well as by site-specific phospho-antibodies. Importantly, the phosphorylation of PHLPP1 was observed to be augmented in presence ER stress inducers like tunicamycin and in the skeletal muscle of diabetic animal models like ob/ob mice and HSD rat. Thus, we conclude PHLPP1 as a bonafide substrate of ERK1/2 with Ser932 as the novel phospho-acceptor site which is influenced by ER stress. Chapter-5Consequences of ERK1/2-mediated PHLPP phosphorylation10323982960Key findings: ERK1/2 mediated PHLPP1 phosphorylation at Ser932 enhances its Cellular functionalityCatalytic activity Substrate interaction5.1 Impact of ERK1/2-mediated PHLPP1 phosphorylation on its cellular functions5.1.1 Effect of p-PHLPP1 on induction of ER stress ER stress induces insulin resistance via an inhibitory crosstalk between ERK signalling and AMPK activity in L6 myotubes 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 337. As PHLPP1is a substrate of ERK1/2 that suppresses AMPK phosphorylation, we hypothesized that PHLPP1 may mediate ERK1/2 dependent inhibition of AMPK in skeletal muscle. Hence, we first studied the effect of ERK1/2 mediated PHLPP1 phosphorylation on the activation of AMPK and induction of ER stress, followed by insulin sensitivity. We over-expressed SFB-PHLPP1? WT and Ser932 mutants in mouse myoblast and analysed the expression of ER stress markers by western blotting. GFP was used as the transfection control. A persistent reduction in the phosphorylation of AMPK and its substrate ACC were observed upon over-expression of PHLPP1? (WT) compared to GFP-transfected cells, while ectopic expression of PHLPP1?S932A (phospho-deficient mutant) failed to inhibit the phosphorylation of AMPK and ACC. The phospho-mimic mutant of PHLPP1? (PHLPP1?S932D) acted similarly to the wild type (Figure 5.1 A). However, the phosphorylation of LKB1 was unaltered by the overexpression of PHLPP1? WT or its mutants. Since, PHLPP1 facilitates ER stress response by inhibition of AMPK we observed a similar trend in the signals of ER stress-responsive markers like BIP, CHOP, p-PERK, and p-eIF2? as that of p-AMPK. Forced expression of PHLPP1? wild-type and Ser932 Asp mutant but not Ser932Ala mutant, activated ER stress responses in wild-type and phosphomimetic mutant transfected cells (Figure 5.1 B). Thus, we concluded negative charge at Ser932 residue is crucial for PHLPP1 mediated ER stress response in cells.5.1.2 Effect of p-PHLPP1 on skeletal muscle insulin resistanceAs the phosphorylation of PHLPP1 at Ser932 residue was enhanced in insulin-resistant animals, we envisaged that ERK1/2 mediated PHLPP1 phosphorylation might influence the inhibitory role of PHLPP1 upon glucose uptake. To assess, we first examined the influence of PHLPP1 mutations on the phosphorylation status of Akt, the key regulator of insulin-dependent glucose uptake. Interestingly, phosphorylation of PHLPP1? at Ser932 displayed a similar influence on insulin-stimulated Akt phosphorylation at Ser473 asAMPK phosphorylation (Figure 5.1 C inset). Subsequently, we studied the effect of Ser932 phosphorylation of PHLPP1 on insulin-mediated glucose uptake, by transfected L6 myoblast with the wild-type or Ser932 mutants of PHLPP1 and measured glucose uptake activity of the cells using 2-NBDG. Consistent with literature and our initial observation, forced expression of wild-type PHLPP1 significantly decreased myoblast glucose uptake, while mutation of Ser932 to Ala partially impaired the ability of PHLPP1? to suppress insulin-stimulated glucose uptake. Interestingly, the phospho-mimic mutant of PHLPP1? retained its ability to inhibit insulin-stimulated glucose uptake (Figure 5.1 C). In addition, Ser932 phosphorylation of PHLPP1 also affected the expression of GLUT4, the key glucose transporter in skeletal muscle. Forced expression of WT or phospho-mimic mutant but not the phospho-deficient mutant of PHLPP1? enhanced protein levels of HDAC5 with a parallel decrease in GLUT4 protein levels in WT and phospho-mimic over-expressing C2C12 cells. However, forced expression of PHLPP1? or its mutants did not alter the levels of HDAC3 and GLUT1 (Figure 5.1 D). Taken together, the findings emphasize the significance of the negative charge at Ser932 residue of PHLPP1. Figure 5.1:Ser932 PHLPP1? phosphorylation is required for ER stress induction and inhibition of insulin-stimulated glucose uptake. (A, B, D) Western blotting using indicated antibodies in C2C12 mouse myoblasts over-expressing SFB-PHLPP1? wild-type and Ser932 mutants, with GFP plasmid as vector control. Densitometric analysis of western blot signals of figure (A) and (D) was performed followed by statistical analysis using one way ANOVA followed by Dunnett’s multiple comparisons test. ap<0.05, bp<0.01, cp<0.005, dp<0.001 vs GFP control. ns, non-significant vs corresponding GFP control. Data are represented as mean+SEM. (C) Uptake of 2-NBDG by L6 myoblasts overexpressing SFB-PHLPP1? wild-type and Ser932 mutants upon insulin stimulates of 5 minutes and 10 minutes. pcDNA3.1 transfected myoblasts were used as internal control. Statistical analysis was performed using one way ANOVA followed by Bonferroni post-hoc test. ns: non-significant, ****p<.001 vs corresponding control transfected cells, $ p<0.001 vs corresponding SFB-PHLPP1? transfected cells. ns, non-significant vs corresponding vector control transfected cells. 5.2.Impact of ERK1/2 on the catalytic activity of PHLPP1 Having observed the functional significance of Ser932 phosphorylation of PHLPP1 at the cellular level, we next assessed the effect of PHLPP1 phosphorylation on its catalytic activity. In vitro phosphatase assay was performed using HEK-293T purified SFB-PHLPP1? wild-type and phosphorylated commercially sourced recombinant AMPK protein. SFB-PH-LRR, a truncated mutant of PHLPP1 lacking the catalytic domain was used as the negative control. An enhanced dephosphorylation of AMPK was detected upon incubation with SFB-PHLPP1? enriched from Raf-BXB transfected HEK-293T cells than SFB-PHLPP1? purified from vector-transfected cells, while a minimal change in pAMPK levels was observed with SFB-PH-LRR both in presence or absence of Raf-BXB (Figure 5.2A). Further, we performed in vitro dephosphorylation assay using wild-type SFB-PHLPP1? and its SFB-Ser932 mutants purified from HEK 293T cells co-expressing Raf-BXB. Here, we observed that wild-type and phospho-mimic mutant significantly dephosphorylated AMPK at Thr172, while the activity of phospho-deficient mutant of PHLPP1? towards rAMPK was reduced (Figure 5.2 B). Thus, we conclude that Ser932 phosphorylation of PHLPP1? enhances its catalytic activity.Figure 5.2: ERK1/2 mediated PHLPP1 phosphorylation augments its catalytic activity. In vitro phosphatase assay of PHLPP1 using rAMPK as substrate and HEK-293T purified SFB-PHLPP1? with and without co-expressing Raf-BXB was used enzyme in (A), while SFB-PHLPP1? WT and Ser932 mutants purified from HEK-293T cells co-transfected with RafBXB in (B). 5.3.Impact of ERK1/2-mediated PHLPP1 upon substrate interaction As the interaction of PHLPP1 with AMPK was observed to be influenced by ER stress (Figure 3.2 D), which promotes ERK1/2 induced PHLPP1 phosphorylation, we assessed the interaction of PHLPP1? and its mutants with AMPK in the presence or absence of tunicamycin. Consistent with our previous observations, the complex formation of wild-type PHLPP1 with AMPK and Akt was enhanced with tunicamycin treatment, while the interaction of phospho-deficient mutant of PHLPP1? with AMPK or Akt was minimally altered by tunicamycin (Figure 5.3), consistent with its inability to dephosphorylate AMPK (Figure 5.1 A). Interestingly, the interaction of phospho-mimetic mutant of PHLPP1? with AMPK or Akt was basally strengthened compared to that of PHLPP1? (WT) and was nominally altered upon treatment with tunicamycin suggesting that the Ser932 phosphorylation of PHLPP1? may enhance its binding with its substrates. Figure 5.3:Ser932 phosphorylation of PHLPP1? promotes substrate interaction. Western blot analysis of affinity purifiedPHLPP1? or its mutants from tunicamycin (5 µg/ml for 3h) treated myoblasts with the indicated antibodies.5.4.Impact of ERK1- mediated PHLPP phosphorylation on its protein stabilityIt was noted previously that over-expression of Raf-BXB enhanced both the phosphorylation as well as expression levels of wild-type PHLPP1. So it was interesting for us to check if the Ser932 phosphorylation of PHLPP1 has any impact on the stability of the protein. We overexpressed wild-type SFB-PHLPP1? and its Ser932 mutants in HEK-293T and checked for the expression of PHLPP1 by western blotting. Inconsistent with our previous observations, upon mutation of Ser 932 to Ala or Asp abolished the Raf-BXB dependent phosphorylation of PHLPP1, but the increase in the expression of total PHLPP1 protein persisted (Figure 5.4), indicating that ERK1/2 mediated PHLPP1 phosphorylation at the Ser932 position is independent of Raf-BXB induced PHLPP1 protein stability. A probable explanation might be the presence of another sub-optimal ERK1/2 phosphorylation site on PHLPP1 that influences its stability or due to inhibition of GSK3?/?-TrCP mediated PHLPP1 degradation upon activation of the MEK1/ERK pathway 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 420, 525. Figure 5.4:Enhanced expression of PHLPP1 is independent of phosphorylation at Ser932. HEK 293T cells were co-transfected with wild and mutant SFB-PHLPP1?. Post 24 h of transfection the cells were lysed and samples were analysed by western blotting with indicated antibodies. ?-actin was used as the loading control.5.5.SummaryThe significance of the Ser932 phosphorylation of PHLPP1 in promoting cellular responses is depicted by the phospho deficient mutant which fails to promote PHLPP1 facilitated ER stress and inhibition of glucose uptake. Further, Ser932 phosphorylation of PHLPP1 was observed to be essential for the catalytic activity of PHLPP1 and interactions with its substrates. Thus collectively, we conclude that ERK1/2 mediated phosphorylation of PHLPP1 enhances its catalytic activity promoting ER stress response and impaired insulin-stimulated glucose uptake by skeletal muscle through AMPK inhibition.Chapter-6Discussion and Future PerspectivesType 2 diabetes (T2D), obesity and metabolic disorders are posing serious health problems that are reaching epidemic proportions in India ADDIN EN.CITE <EndNote><Cite><Author>Kaveeshwar</Author><Year>2014</Year><RecNum>468</RecNum><DisplayText>526</DisplayText><record><rec-number>468</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>468</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Kaveeshwar, S. A.</author><author>Cornwall, J.</author></authors></contributors><auth-address>Bangalore, India. University of Otago.</auth-address><titles><title>The current state of diabetes mellitus in India</title><secondary-title>Australas Med J</secondary-title><alt-title>The Australasian medical journal</alt-title></titles><periodical><full-title>Australas Med J</full-title><abbr-1>The Australasian medical journal</abbr-1></periodical><alt-periodical><full-title>Australas Med J</full-title><abbr-1>The Australasian medical journal</abbr-1></alt-periodical><pages>45-8</pages><volume>7</volume><number>1</number><dates><year>2014</year></dates><isbn>1836-1935 (Print) 1836-1935 (Linking)</isbn><accession-num>24567766</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24567766</url></related-urls></urls><custom2>3920109</custom2><electronic-resource-num>10.4066/AMJ.2013.1979</electronic-resource-num></record></Cite></EndNote>526. Insulin resistance (IR) is critical in the development and progression of diabetes mellitus; it subdues the efficacy of the glucose uptake in the target tissue and its metabolism in response to insulin stimulus 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ADDIN EN.CITE.DATA 527, 528. Over the past decade, numerous lines of evidence have clearly demonstrated that activation of ER stress due to sustained chronic inflammation along with metabolic imbalance (hyperglycemia and dyslipidemia) leads to altered insulin responses <EndNote><Cite><Author>Ozcan</Author><Year>2004</Year><RecNum>26</RecNum><DisplayText>[142, 474, 529]</DisplayText><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozcan, U.</author><author>Cao, Q.</author><author>Yilmaz, E.</author><author>Lee, A. H.</author><author>Iwakoshi, N. N.</author><author>Ozdelen, E.</author><author>Tuncman, G.</author><author>Gorgun, C.</author><author>Glimcher, L. H.</author><author>Hotamisligil, G. S.</author></authors></contributors><auth-address>Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA.</auth-address><titles><title>Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes</title><secondary-title>Science</secondary-title><alt-title>Science</alt-title></titles><periodical><full-title>Science</full-title><abbr-1>Science</abbr-1></periodical><alt-periodical><full-title>Science</full-title><abbr-1>Science</abbr-1></alt-periodical><pages>457-61</pages><volume>306</volume><number>5695</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Animals</keyword><keyword>Cells, Cultured</keyword><keyword>DNA-Binding Proteins/genetics/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Homeostasis</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>*Insulin Resistance</keyword><keyword>Liver/metabolism</keyword><keyword>Membrane Proteins/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Inbred BALB C</keyword><keyword>Mice, Obese</keyword><keyword>Mitogen-Activated Protein Kinase 8</keyword><keyword>Mitogen-Activated Protein Kinases/metabolism</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Mutation</keyword><keyword>Nuclear Proteins/genetics/metabolism</keyword><keyword>Obesity/*metabolism</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword><keyword>Rats</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Regulatory Factor X Transcription Factors</keyword><keyword>Signal Transduction</keyword><keyword>Transcription Factors</keyword><keyword>Tunicamycin/pharmacology</keyword><keyword>X-Box Binding Protein 1</keyword><keyword>eIF-2 Kinase/metabolism</keyword></keywords><dates><year>2004</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>1095-9203 (Electronic)&#xD;0036-8075 (Linking)</isbn><accession-num>15486293</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15486293</url></related-urls></urls><electronic-resource-num>10.1126/science.1103160</electronic-resource-num></record></Cite><Cite><Author>Nakatani</Author><Year>2005</Year><RecNum>471</RecNum><record><rec-number>471</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">471</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nakatani, Y.</author><author>Kaneto, H.</author><author>Kawamori, D.</author><author>Yoshiuchi, K.</author><author>Hatazaki, M.</author><author>Matsuoka, T. A.</author><author>Ozawa, K.</author><author>Ogawa, S.</author><author>Hori, M.</author><author>Yamasaki, Y.</author><author>Matsuhisa, M.</author></authors></contributors><auth-address>Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.</auth-address><titles><title>Involvement of endoplasmic reticulum stress in insulin resistance and diabetes</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>847-51</pages><volume>280</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>*Diabetes Mellitus, Type 2/etiology/metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Glucose Tolerance Test</keyword><keyword>HSP70 Heat-Shock Proteins</keyword><keyword>*Insulin Resistance</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Obese</keyword><keyword>Proteins/*metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Jan 7</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>15509553</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15509553</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M411860200</electronic-resource-num></record></Cite><Cite><Author>Flamment</Author><Year>2012</Year><RecNum>40</RecNum><record><rec-number>40</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">40</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Flamment, M.</author><author>Hajduch, E.</author><author>Ferre, P.</author><author>Foufelle, F.</author></authors></contributors><auth-address>Institut National de la Sante et de la Recherche Medicale (INSERM), Centre de Recherche des Cordeliers, Unite Mixte de Recherche en Sante (UMR-S) 872, Paris, F-75006 France.</auth-address><titles><title>New insights into ER stress-induced insulin resistance</title><secondary-title>Trends Endocrinol Metab</secondary-title><alt-title>Trends in endocrinology and metabolism: TEM</alt-title></titles><periodical><full-title>Trends Endocrinol Metab</full-title><abbr-1>Trends in endocrinology and metabolism: TEM</abbr-1></periodical><alt-periodical><full-title>Trends Endocrinol Metab</full-title><abbr-1>Trends in endocrinology and metabolism: TEM</abbr-1></alt-periodical><pages>381-90</pages><volume>23</volume><number>8</number><keywords><keyword>Adipose Tissue/physiopathology</keyword><keyword>Diabetes Mellitus, Type 2</keyword><keyword>Endoplasmic Reticulum Stress/*physiology</keyword><keyword>Humans</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Lipid Metabolism</keyword><keyword>Liver/physiopathology</keyword><keyword>Muscle, Skeletal/physiopathology</keyword><keyword>Obesity</keyword><keyword>Signal Transduction</keyword><keyword>Transcription Factors/physiology</keyword><keyword>Unfolded Protein Response/*physiology</keyword></keywords><dates><year>2012</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1879-3061 (Electronic)&#xD;1043-2760 (Linking)</isbn><accession-num>22770719</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22770719</url></related-urls></urls><electronic-resource-num>10.1016/j.tem.2012.06.003</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Ozcan</Author><Year>2004</Year><RecNum>26</RecNum><DisplayText>[142, 474, 529]</DisplayText><record><rec-number>26</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">26</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozcan, U.</author><author>Cao, Q.</author><author>Yilmaz, E.</author><author>Lee, A. H.</author><author>Iwakoshi, N. N.</author><author>Ozdelen, E.</author><author>Tuncman, G.</author><author>Gorgun, C.</author><author>Glimcher, L. H.</author><author>Hotamisligil, G. S.</author></authors></contributors><auth-address>Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA.</auth-address><titles><title>Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes</title><secondary-title>Science</secondary-title><alt-title>Science</alt-title></titles><periodical><full-title>Science</full-title><abbr-1>Science</abbr-1></periodical><alt-periodical><full-title>Science</full-title><abbr-1>Science</abbr-1></alt-periodical><pages>457-61</pages><volume>306</volume><number>5695</number><keywords><keyword>Adipose Tissue/metabolism</keyword><keyword>Animals</keyword><keyword>Cells, Cultured</keyword><keyword>DNA-Binding Proteins/genetics/metabolism</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Homeostasis</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Receptor Substrate Proteins</keyword><keyword>*Insulin Resistance</keyword><keyword>Liver/metabolism</keyword><keyword>Membrane Proteins/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Inbred BALB C</keyword><keyword>Mice, Obese</keyword><keyword>Mitogen-Activated Protein Kinase 8</keyword><keyword>Mitogen-Activated Protein Kinases/metabolism</keyword><keyword>Muscle, Skeletal/metabolism</keyword><keyword>Mutation</keyword><keyword>Nuclear Proteins/genetics/metabolism</keyword><keyword>Obesity/*metabolism</keyword><keyword>Phosphoproteins/metabolism</keyword><keyword>Phosphorylation</keyword><keyword>Protein-Serine-Threonine Kinases/metabolism</keyword><keyword>Rats</keyword><keyword>Receptor, Insulin/metabolism</keyword><keyword>Regulatory Factor X Transcription Factors</keyword><keyword>Signal Transduction</keyword><keyword>Transcription Factors</keyword><keyword>Tunicamycin/pharmacology</keyword><keyword>X-Box Binding Protein 1</keyword><keyword>eIF-2 Kinase/metabolism</keyword></keywords><dates><year>2004</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>1095-9203 (Electronic)&#xD;0036-8075 (Linking)</isbn><accession-num>15486293</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15486293</url></related-urls></urls><electronic-resource-num>10.1126/science.1103160</electronic-resource-num></record></Cite><Cite><Author>Nakatani</Author><Year>2005</Year><RecNum>471</RecNum><record><rec-number>471</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">471</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nakatani, Y.</author><author>Kaneto, H.</author><author>Kawamori, D.</author><author>Yoshiuchi, K.</author><author>Hatazaki, M.</author><author>Matsuoka, T. A.</author><author>Ozawa, K.</author><author>Ogawa, S.</author><author>Hori, M.</author><author>Yamasaki, Y.</author><author>Matsuhisa, M.</author></authors></contributors><auth-address>Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.</auth-address><titles><title>Involvement of endoplasmic reticulum stress in insulin resistance and diabetes</title><secondary-title>J Biol Chem</secondary-title><alt-title>The Journal of biological chemistry</alt-title></titles><periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></periodical><alt-periodical><full-title>J Biol Chem</full-title><abbr-1>The Journal of biological chemistry</abbr-1></alt-periodical><pages>847-51</pages><volume>280</volume><number>1</number><keywords><keyword>Animals</keyword><keyword>*Diabetes Mellitus, Type 2/etiology/metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Glucose Tolerance Test</keyword><keyword>HSP70 Heat-Shock Proteins</keyword><keyword>*Insulin Resistance</keyword><keyword>Liver/metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Obese</keyword><keyword>Proteins/*metabolism</keyword></keywords><dates><year>2005</year><pub-dates><date>Jan 7</date></pub-dates></dates><isbn>0021-9258 (Print)&#xD;0021-9258 (Linking)</isbn><accession-num>15509553</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15509553</url></related-urls></urls><electronic-resource-num>10.1074/jbc.M411860200</electronic-resource-num></record></Cite><Cite><Author>Flamment</Author><Year>2012</Year><RecNum>40</RecNum><record><rec-number>40</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">40</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Flamment, M.</author><author>Hajduch, E.</author><author>Ferre, P.</author><author>Foufelle, F.</author></authors></contributors><auth-address>Institut National de la Sante et de la Recherche Medicale (INSERM), Centre de Recherche des Cordeliers, Unite Mixte de Recherche en Sante (UMR-S) 872, Paris, F-75006 France.</auth-address><titles><title>New insights into ER stress-induced insulin resistance</title><secondary-title>Trends Endocrinol Metab</secondary-title><alt-title>Trends in endocrinology and metabolism: TEM</alt-title></titles><periodical><full-title>Trends Endocrinol Metab</full-title><abbr-1>Trends in endocrinology and metabolism: TEM</abbr-1></periodical><alt-periodical><full-title>Trends Endocrinol Metab</full-title><abbr-1>Trends in endocrinology and metabolism: TEM</abbr-1></alt-periodical><pages>381-90</pages><volume>23</volume><number>8</number><keywords><keyword>Adipose Tissue/physiopathology</keyword><keyword>Diabetes Mellitus, Type 2</keyword><keyword>Endoplasmic Reticulum Stress/*physiology</keyword><keyword>Humans</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Lipid Metabolism</keyword><keyword>Liver/physiopathology</keyword><keyword>Muscle, Skeletal/physiopathology</keyword><keyword>Obesity</keyword><keyword>Signal Transduction</keyword><keyword>Transcription Factors/physiology</keyword><keyword>Unfolded Protein Response/*physiology</keyword></keywords><dates><year>2012</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1879-3061 (Electronic)&#xD;1043-2760 (Linking)</isbn><accession-num>22770719</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/22770719</url></related-urls></urls><electronic-resource-num>10.1016/j.tem.2012.06.003</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 142, 474, 529. However, to date majority of reports have emphasized the impact of ER stress on adipose tissue and liver 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 ADDIN EN.CITE 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ADDIN EN.CITE.DATA 530-532, but its influence in dismantling the glucose uptake machinery in the skeletal muscle 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 142, the major site for whole body glucose metabolism, is less studied. The ER is one of the largest cytoplasmic organelles in mammalian cells that regulate intracellular calcium storage, lipid biosynthesis, and protein folding and its transport 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 533. Activation of the cellular response to ER stress, which has been termed the unfolded protein response (UPR), consists of 3 main signalling cascades initiated by three ER transmembrane proteins: PKR-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol requiring enzyme 1 (IRE1) 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Under ER stress, BiP (the major chaperone in ER) dissociates from the ER-resident transmembrane proteins, activates the UPR to restore ER homeostasis ADDIN EN.CITE <EndNote><Cite><Author>Schroder</Author><Year>2005</Year><RecNum>475</RecNum><DisplayText>219</DisplayText><record><rec-number>475</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>475</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Schroder, M.</author><author>Kaufman, R. J.</author></authors></contributors><auth-address>School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK.</auth-address><titles><title>ER stress and the unfolded protein response</title><secondary-title>Mutat Res</secondary-title><alt-title>Mutation research</alt-title></titles><periodical><full-title>Mutat Res</full-title><abbr-1>Mutation research</abbr-1></periodical><alt-periodical><full-title>Mutat Res</full-title><abbr-1>Mutation research</abbr-1></alt-periodical><pages>29-63</pages><volume>569</volume><number>1-2</number><keywords><keyword>Animals</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Metabolic Diseases/metabolism</keyword><keyword>Molecular Chaperones/metabolism</keyword><keyword>*Oxidative Stress</keyword><keyword>*Protein Folding</keyword><keyword>Signal Transduction/*physiology</keyword></keywords><dates><year>2005</year><pub-dates><date>Jan 6</date></pub-dates></dates><isbn>0027-5107 (Print) 0027-5107 (Linking)</isbn><accession-num>15603751</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/15603751</url></related-urls></urls><electronic-resource-num>10.1016/j.mrfmmm.2004.06.056</electronic-resource-num></record></Cite></EndNote>219. PERK activation phosphorylates eIF2?, which activates C/EBP and ATF4 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ADDIN EN.CITE 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 ADDIN EN.CITE.DATA 235, 535. Similarly, IRE-1 splices XBP1 mRNA leading to more active sXBP1 protein 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 536. sXBP1, ATF6 and C/EBP along with ATF4 and CHOP (co-regulator) up-regulates several genes like Trb3, a pseudo-kinase that dampens Akt signalling in muscle by binding to its phospho-pocket 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 537. Also, IRE1 and PERK limits the action of insulin by JNK1/2 and IKK? mediated phosphorylation of insulin receptor substrate (IRS) at Ser307 in the liver and adipose tissue, which hampers the insulin signalling 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 142, 538, 539. Conversely, genetic alleviation of ER chaperone BiP in the liver of ob/ob mice 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 307 or pharmacological administration of chemical chaperone-like 4-PBA (4-phenyl butyric acid) mice enhanced insulin sensitivity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 512. Importantly, gastric bypass surgery for weight reduction led to a decrease in hepatic ER stress and improved insulin sensitivity in obese humans 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 146. Based on the aforementioned, ER stress-activated cellular response can hamper the insulin signalling leading to IR, yet, a handful of information is available about the molecular phosphatases that regulate ER stress driven IR. A recent study noted that activity of the ER resident phosphatase PTP1B was enhanced under ER stress, impairing the insulin-stimulated tyrosine phosphorylation of both insulin receptor and IRS1 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 342. Similarly, SKIP, a PIP3 phosphatase, was reported to be up-regulated upon ER stress in cultured skeletal muscle cells which reduced PI3K signalling thereby inhibiting insulin-stimulated glucose uptake 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 346. However, to the best of our knowledge, no phosphatase(s) is/are reported that could directly dephosphorylate insulin-induced Akt at Ser473 or insulin-independent AMPK at Thr172 (the master regulators of insulin sensitivity) under prolonged ER stress.PHLPP1 as insulin resistance marker: PHLPP1 was identified as the phosphatase that direct dephosphorylates Akt at the hydrophobic phospho-motif Ser473 to inactivate it 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 58. Due to its association with Akt dephosphorylation, PHLPP1 has been speculated as a therapeutic target for IR related diseases in multiple reviews 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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IcmliYWw8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNOdW0+MTA8L1JlY051bT48RGlzcGxheVRleHQ+WzUxNSwgNTQwLCA1NDFdPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0icGR0c2F2ZWQ3cHB3cjBlMHMycXZ6MnpmMHd4cngyeGQwYWF2Ij4xMDwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+SHJpYmFsLCBNLiBMLjwvYXV0aG9yPjxhdXRob3I+TWFuY3VzbywgRS48L2F1dGhvcj48YXV0aG9yPlNwaWdhLCBSLjwvYXV0aG9yPjxhdXRob3I+TWFubmlubywgRy4gQy48L2F1dGhvcj48YXV0aG9yPkZpb3JlbnRpbm8sIFQuIFYuPC9hdXRob3I+PGF1dGhvcj5BbmRyZW96emksIEYuPC9hdXRob3I+PGF1dGhvcj5TZXN0aSwgRy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5hIERlcGFydG1lbnQgb2YgTWVkaWNhbCBhbmQgU3VyZ2ljYWwgU2NpZW5jZXMgLCBVbml2ZXJzaXR5IE1hZ25hIEdyYWVjaWEgb2YgQ2F0YW56YXJvICwgQ2F0YW56YXJvICwgSXRhbHkuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+UEhMUFAgcGhvc3BoYXRhc2VzIGFzIGEgdGhlcmFwZXV0aWMgdGFyZ2V0IGluIGluc3VsaW4gcmVzaXN0YW5jZS1yZWxhdGVkIGRpc2Vhc2VzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkV4cGVydCBPcGluIFRoZXIgVGFyZ2V0czwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+RXhwZXJ0IG9waW5pb24gb24gdGhlcmFwZXV0aWMgdGFyZ2V0czwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkV4cGVydCBPcGluIFRoZXIgVGFyZ2V0czwvZnVsbC10aXRsZT48YWJici0xPkV4cGVydCBvcGluaW9uIG9uIHRoZXJhcGV1dGljIHRhcmdldHM8L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkV4cGVydCBPcGluIFRoZXIgVGFyZ2V0czwvZnVsbC10aXRsZT48YWJici0xPkV4cGVydCBvcGluaW9uIG9uIHRoZXJhcGV1dGljIHRhcmdldHM8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz42NjMtNzU8L3BhZ2VzPjx2b2x1bWU+MjA8L3ZvbHVtZT48bnVtYmVyPjY8L251bWJlcj48a2V5d29yZHM+PGtleXdvcmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5HZW5lIEV4cHJlc3Npb24gUmVndWxhdGlvbjwva2V5d29yZD48a2V5d29yZD5HZW5ldGljIFZhcmlhdGlvbjwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+SW5zdWxpbi8qbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD4qSW5zdWxpbiBSZXNpc3RhbmNlPC9rZXl3b3JkPjxrZXl3b3JkPk1vbGVjdWxhciBUYXJnZXRlZCBUaGVyYXB5PC9rZXl3b3JkPjxrZXl3b3JkPk5lb3BsYXNtcy9kcnVnIHRoZXJhcHkvcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPk51Y2xlYXIgUHJvdGVpbnMvZ2VuZXRpY3MvKm1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+UGhvc3Bob3Byb3RlaW4gUGhvc3BoYXRhc2VzL2dlbmV0aWNzLyptZXRhYm9saXNtPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTY8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5KdW48L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4xNzQ0LTc2MzEgKEVsZWN0cm9uaWMpJiN4RDsxNDcyLTgyMjIgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjI2NjUyMTgyPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzI2NjUyMTgyPC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xNTE3LzE0NzI4MjIyLjIwMTYuMTEzMDgyMjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+TWF0aHVyPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVjTnVtPjExPC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4xMTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9InBkdHNhdmVkN3Bwd3IwZTBzMnF2ejJ6ZjB3eHJ4MnhkMGFhdiI+MTE8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPk1hdGh1ciwgQS48L2F1dGhvcj48YXV0aG9yPlBhbmRleSwgVi4gSy48L2F1dGhvcj48YXV0aG9yPktha2thciwgUC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5IZXJiYWwgUmVzZWFyY2ggTGFib3JhdG9yeUNTSVItSW5kaWFuIEluc3RpdHV0ZSBvZiBUb3hpY29sb2d5IFJlc2VhcmNoLCBMdWNrbm93LCBJbmRpYS4mI3hEO0JhYnUgQmFuYXJhc2kgRGFzIFVuaXZlcnNpdHlCQkQgQ2l0eSwgTHVja25vdywgSW5kaWEuJiN4RDtBY2FkZW15IG9mIFNjaWVudGlmaWMgYW5kIElubm92YXRpdmUgUmVzZWFyY2hDU0lSLUlJVFIsIEx1Y2tub3csIEluZGlhLiYjeEQ7SGVyYmFsIFJlc2VhcmNoIExhYm9yYXRvcnlDU0lSLUluZGlhbiBJbnN0aXR1dGUgb2YgVG94aWNvbG9neSBSZXNlYXJjaCwgTHVja25vdywgSW5kaWEgcGtha2thckBpaXRyLnJlcy5pbi48L2F1dGgtYWRkcmVzcz48dGl0bGVzPjx0aXRsZT5QSExQUDogYSBwdXRhdGl2ZSBjZWxsdWxhciB0YXJnZXQgZHVyaW5nIGluc3VsaW4gcmVzaXN0YW5jZSBhbmQgdHlwZSAyIGRpYWJldGVzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkogRW5kb2NyaW5vbDwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+VGhlIEpvdXJuYWwgb2YgZW5kb2NyaW5vbG9neTwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkogRW5kb2NyaW5vbDwvZnVsbC10aXRsZT48YWJici0xPlRoZSBKb3VybmFsIG9mIGVuZG9jcmlub2xvZ3k8L2FiYnItMT48L3BlcmlvZGljYWw+PGFsdC1wZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkogRW5kb2NyaW5vbDwvZnVsbC10aXRsZT48YWJici0xPlRoZSBKb3VybmFsIG9mIGVuZG9jcmlub2xvZ3k8L2FiYnItMT48L2FsdC1wZXJpb2RpY2FsPjxwYWdlcz5SMTg1LVIxOTg8L3BhZ2VzPjx2b2x1bWU+MjMzPC92b2x1bWU+PG51bWJlcj4zPC9udW1iZXI+PGRhdGVzPjx5ZWFyPjIwMTc8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5KdW48L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4xNDc5LTY4MDUgKEVsZWN0cm9uaWMpJiN4RDswMDIyLTA3OTUgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjI4NDI4MzYzPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzI4NDI4MzYzPC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xNTMwL0pPRS0xNy0wMDgxPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5PJmFwb3M7TmVpbGw8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxSZWNOdW0+MzU5PC9SZWNOdW0+PHJlY29yZD48cmVjLW51bWJlcj4zNTk8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5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ADDIN EN.CITE.DATA 515, 540, 541 and our current observation further strengthen this line of thought. Increased expression of PHLPP1, but not PHLPP2, in the adipose and skeletal muscle of obese and diabetic patients was reported by Andreozzi et al 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 459 and Cozzone et al 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 463 supported the speculation. Consistently, we also observed an enhanced expression of PHLPP1 in our pre-clinical animal models (HFD, HSD, ob/ob) associated with insulin resistance. In addition, consistent with previous reports 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ADDIN EN.CITE.DATA 87, 467, ER stress markers like BiP and CHOP were also enhanced in the same samples. Underscoring the key role of PHLPP1 in normal physiology, knockdown of PHLPP1 in the skeletal muscle of WT mice improved whole body glucose metabolism along with improved insulin sensitivity. Thus, we conclude PHLPP1 to play an important role in controlling the whole body glucose metabolism and insulin sensitivity. PHLPP regulates ER stress:In the present study, we identified PHLPP1 as a vital player of ER stress cellular response. A significant reduction in tunicamycin-induced expression of ER stress markers CHOP, sXBP1 and Trb3 was detected in both cultured myotubes and animals upon ablations of PHLPP1, while notably, ectopic expression of PHLPP1 by itself (in absence of any chemical/physiological inducers) was sufficient to activate ER stress signalling, indicating the significance of PHLPP1 in the induction/progression of ER stress. This could be probably due to the impact of PHLPP1 on mitochondrial functionality. Loss of PHLPP1 was shown to deregulate mitochondrial respiration in colon cancer cell lines 32. It is well documented that mitochondria dysfunction and ER stress play a critical role in IR development. In fact, ER and mitochondria cooperate via cross-talk through structural and functional networks to maintain cellular homeostasis 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ADDIN EN.CITE.DATA 542, 543. However, understanding the molecular insights leading to these individual disorders and how they are linked has been challenging. The complex nature of mitochondrial and ER lumen functions in context of IR has been speculated by number of theories, with a few opposing views. Recent studies show that alteration in calcium level disturbs calcium dependent signaling pathway that impedes insulin signaling resulting in IR <EndNote><Cite><Author>Gutierrez</Author><Year>2014</Year><RecNum>676</RecNum><DisplayText>[544, 545]</DisplayText><record><rec-number>676</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">676</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gutierrez, T.</author><author>Parra, V.</author><author>Troncoso, R.</author><author>Pennanen, C.</author><author>Contreras-Ferrat, A.</author><author>Vasquez-Trincado, C.</author><author>Morales, P. E.</author><author>Lopez-Crisosto, C.</author><author>Sotomayor-Flores, C.</author><author>Chiong, M.</author><author>Rothermel, B. A.</author><author>Lavandero, S.</author></authors></contributors><auth-address>Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. tomasg@bq.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. Valentina.Parra@utsouthwestern.edu.&#xD;Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, 75390-8573, USA. Valentina.Parra@utsouthwestern.edu.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. rtroncoso@inta.uchile.cl.&#xD;Instituto de Nutricion y Tecnologia de los Alimentos (INTA), Universidad de Chile, Santiago, 7830490, Chile. rtroncoso@inta.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. pennanen@ciq.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. acontreras@med.uchile.cl.&#xD;Institute for Research in Dental Science, Faculty of Dentistry, Universidad de Chile, Santiago, 838049, Chile. acontreras@med.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. Cesarvasquez@ug.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. pablomc@um.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. camilalc@ug.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. cristiansotomayorf@yahoo.com.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. mchiong@uchile.cl.&#xD;Centro de Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. mchiong@uchile.cl.&#xD;Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, 75390-8573, USA. Beverly.Rothermel@utsouthwestern.edu.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. slavander@uchile.cl.&#xD;Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, 75390-8573, USA. slavander@uchile.cl.&#xD;Centro de Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. slavander@uchile.cl.</auth-address><titles><title>Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in hypertrophic cardiomyocytes</title><secondary-title>Cell Commun Signal</secondary-title><alt-title>Cell communication and signaling : CCS</alt-title></titles><periodical><full-title>Cell Commun Signal</full-title><abbr-1>Cell communication and signaling : CCS</abbr-1></periodical><alt-periodical><full-title>Cell Commun Signal</full-title><abbr-1>Cell communication and signaling : CCS</abbr-1></alt-periodical><pages>68</pages><volume>12</volume><keywords><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Calcium/*metabolism</keyword><keyword>Calcium Signaling</keyword><keyword>Cardiomegaly/*metabolism</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Inositol 1,4,5-Trisphosphate Receptors/metabolism</keyword><keyword>Insulin/*metabolism</keyword><keyword>Mitochondria, Heart/*metabolism</keyword><keyword>Myocytes, Cardiac/*metabolism</keyword><keyword>Oxygen Consumption</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2014</year><pub-dates><date>Nov 7</date></pub-dates></dates><isbn>1478-811X (Electronic)&#xD;1478-811X (Linking)</isbn><accession-num>25376904</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25376904</url></related-urls></urls><custom2>4234850</custom2><electronic-resource-num>10.1186/s12964-014-0068-4</electronic-resource-num></record></Cite><Cite><Author>Ozcan</Author><Year>2016</Year><RecNum>677</RecNum><record><rec-number>677</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">677</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozcan, L.</author><author>Tabas, I.</author></authors></contributors><auth-address>Department of Medicine, Columbia University, New York, NY, USA. lo2192@columbia.edu.&#xD;Department of Medicine, Columbia University, New York, NY, USA.&#xD;Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA.&#xD;Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.</auth-address><titles><title>Calcium signalling and ER stress in insulin resistance and atherosclerosis</title><secondary-title>J Intern Med</secondary-title><alt-title>Journal of internal medicine</alt-title></titles><periodical><full-title>J Intern Med</full-title><abbr-1>Journal of internal medicine</abbr-1></periodical><alt-periodical><full-title>J Intern Med</full-title><abbr-1>Journal of internal medicine</abbr-1></alt-periodical><pages>457-464</pages><volume>280</volume><number>5</number><keywords><keyword>Animals</keyword><keyword>Atherosclerosis/*metabolism</keyword><keyword>Calcium Signaling/*physiology</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>Diabetic Angiopathies/*metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin Resistance/*physiology</keyword></keywords><dates><year>2016</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1365-2796 (Electronic)&#xD;0954-6820 (Linking)</isbn><accession-num>27739133</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/27739133</url></related-urls></urls><custom2>5083967</custom2><electronic-resource-num>10.1111/joim.12562</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Gutierrez</Author><Year>2014</Year><RecNum>676</RecNum><DisplayText>[544, 545]</DisplayText><record><rec-number>676</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">676</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gutierrez, T.</author><author>Parra, V.</author><author>Troncoso, R.</author><author>Pennanen, C.</author><author>Contreras-Ferrat, A.</author><author>Vasquez-Trincado, C.</author><author>Morales, P. E.</author><author>Lopez-Crisosto, C.</author><author>Sotomayor-Flores, C.</author><author>Chiong, M.</author><author>Rothermel, B. A.</author><author>Lavandero, S.</author></authors></contributors><auth-address>Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. tomasg@bq.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. Valentina.Parra@utsouthwestern.edu.&#xD;Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, 75390-8573, USA. Valentina.Parra@utsouthwestern.edu.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. rtroncoso@inta.uchile.cl.&#xD;Instituto de Nutricion y Tecnologia de los Alimentos (INTA), Universidad de Chile, Santiago, 7830490, Chile. rtroncoso@inta.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. pennanen@ciq.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. acontreras@med.uchile.cl.&#xD;Institute for Research in Dental Science, Faculty of Dentistry, Universidad de Chile, Santiago, 838049, Chile. acontreras@med.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. Cesarvasquez@ug.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. pablomc@um.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. camilalc@ug.uchile.cl.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. cristiansotomayorf@yahoo.com.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. mchiong@uchile.cl.&#xD;Centro de Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. mchiong@uchile.cl.&#xD;Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, 75390-8573, USA. Beverly.Rothermel@utsouthwestern.edu.&#xD;Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Quimicas y Farmaceuticas &amp; Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. slavander@uchile.cl.&#xD;Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, 75390-8573, USA. slavander@uchile.cl.&#xD;Centro de Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago, 838049, Chile. slavander@uchile.cl.</auth-address><titles><title>Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in hypertrophic cardiomyocytes</title><secondary-title>Cell Commun Signal</secondary-title><alt-title>Cell communication and signaling : CCS</alt-title></titles><periodical><full-title>Cell Commun Signal</full-title><abbr-1>Cell communication and signaling : CCS</abbr-1></periodical><alt-periodical><full-title>Cell Commun Signal</full-title><abbr-1>Cell communication and signaling : CCS</abbr-1></alt-periodical><pages>68</pages><volume>12</volume><keywords><keyword>Animals</keyword><keyword>Animals, Newborn</keyword><keyword>Calcium/*metabolism</keyword><keyword>Calcium Signaling</keyword><keyword>Cardiomegaly/*metabolism</keyword><keyword>Endoplasmic Reticulum/metabolism</keyword><keyword>Glucose/metabolism</keyword><keyword>Inositol 1,4,5-Trisphosphate Receptors/metabolism</keyword><keyword>Insulin/*metabolism</keyword><keyword>Mitochondria, Heart/*metabolism</keyword><keyword>Myocytes, Cardiac/*metabolism</keyword><keyword>Oxygen Consumption</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Signal Transduction</keyword></keywords><dates><year>2014</year><pub-dates><date>Nov 7</date></pub-dates></dates><isbn>1478-811X (Electronic)&#xD;1478-811X (Linking)</isbn><accession-num>25376904</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/25376904</url></related-urls></urls><custom2>4234850</custom2><electronic-resource-num>10.1186/s12964-014-0068-4</electronic-resource-num></record></Cite><Cite><Author>Ozcan</Author><Year>2016</Year><RecNum>677</RecNum><record><rec-number>677</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">677</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozcan, L.</author><author>Tabas, I.</author></authors></contributors><auth-address>Department of Medicine, Columbia University, New York, NY, USA. lo2192@columbia.edu.&#xD;Department of Medicine, Columbia University, New York, NY, USA.&#xD;Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA.&#xD;Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.</auth-address><titles><title>Calcium signalling and ER stress in insulin resistance and atherosclerosis</title><secondary-title>J Intern Med</secondary-title><alt-title>Journal of internal medicine</alt-title></titles><periodical><full-title>J Intern Med</full-title><abbr-1>Journal of internal medicine</abbr-1></periodical><alt-periodical><full-title>J Intern Med</full-title><abbr-1>Journal of internal medicine</abbr-1></alt-periodical><pages>457-464</pages><volume>280</volume><number>5</number><keywords><keyword>Animals</keyword><keyword>Atherosclerosis/*metabolism</keyword><keyword>Calcium Signaling/*physiology</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism</keyword><keyword>Diabetic Angiopathies/*metabolism</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Humans</keyword><keyword>Insulin Resistance/*physiology</keyword></keywords><dates><year>2016</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1365-2796 (Electronic)&#xD;0954-6820 (Linking)</isbn><accession-num>27739133</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/27739133</url></related-urls></urls><custom2>5083967</custom2><electronic-resource-num>10.1111/joim.12562</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 544, 545. Few structural studies highlight the importance of abnormalities in the structure and function of MAM (Mitochondria associated ER membrane) in insulin resistance condition <EndNote><Cite><Author>Shinjo</Author><Year>2017</Year><RecNum>678</RecNum><DisplayText>[546, 547]</DisplayText><record><rec-number>678</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">678</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shinjo, S.</author><author>Jiang, S.</author><author>Nameta, M.</author><author>Suzuki, T.</author><author>Kanai, M.</author><author>Nomura, Y.</author><author>Goda, N.</author></authors></contributors><auth-address>Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan; Research Institute for Life Support Innovation, Research Organization for Nano &amp; Life Innovation, Waseda University, Tokyo 162-0041, Japan. Electronic address: stshinjo@gmail.com.&#xD;Niigata College of Medical Technology, Niigata 950-2076, Japan.&#xD;Department of Electron Microscope Core Facility, Niigata University, Niigata 951-8510, Japan.&#xD;Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.&#xD;Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan; School of Creative Science and Engineering, Waseda University, Tokyo 162-8480, Japan.</auth-address><titles><title>Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid-induced insulin resistance</title><secondary-title>Exp Cell Res</secondary-title><alt-title>Experimental cell research</alt-title></titles><periodical><full-title>Exp Cell Res</full-title><abbr-1>Experimental cell research</abbr-1></periodical><alt-periodical><full-title>Exp Cell Res</full-title><abbr-1>Experimental cell research</abbr-1></alt-periodical><pages>86-93</pages><volume>359</volume><number>1</number><keywords><keyword>Endoplasmic Reticulum/drug effects/*metabolism</keyword><keyword>Endoplasmic Reticulum Stress/drug effects</keyword><keyword>Hep G2 Cells</keyword><keyword>Humans</keyword><keyword>Insulin/pharmacology</keyword><keyword>*Insulin Resistance</keyword><keyword>Intracellular Membranes/drug effects/*metabolism</keyword><keyword>Membrane Proteins/metabolism</keyword><keyword>Mitochondria/drug effects/*metabolism</keyword><keyword>Mitochondrial Proteins/metabolism</keyword><keyword>Palmitic Acid/*pharmacology</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword><keyword>Reactive Oxygen Species/metabolism</keyword><keyword>Signal Transduction/drug effects</keyword><keyword>eIF-2 Kinase/metabolism</keyword></keywords><dates><year>2017</year><pub-dates><date>Oct 1</date></pub-dates></dates><isbn>1090-2422 (Electronic)&#xD;0014-4827 (Linking)</isbn><accession-num>28827061</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28827061</url></related-urls></urls><electronic-resource-num>10.1016/j.yexcr.2017.08.006</electronic-resource-num></record></Cite><Cite><Author>Tubbs</Author><Year>2014</Year><RecNum>679</RecNum><record><rec-number>679</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">679</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tubbs, E.</author><author>Theurey, P.</author><author>Vial, G.</author><author>Bendridi, N.</author><author>Bravard, A.</author><author>Chauvin, M. A.</author><author>Ji-Cao, J.</author><author>Zoulim, F.</author><author>Bartosch, B.</author><author>Ovize, M.</author><author>Vidal, H.</author><author>Rieusset, J.</author></authors></contributors><auth-address>INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, INRA U1235, INSA of Lyon, Rockefeller and Charles Merieux Lyon-Sud Medical Universities, Lyon, France.&#xD;INSERM UMR-1052, Cancer Research Center of Lyon, Lyon 1 University, Hospices Civils de Lyon, Lyon, France.&#xD;INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, INRA U1235, INSA of Lyon, Rockefeller and Charles Merieux Lyon-Sud Medical Universities, Lyon, France Hospices Civils de Lyon, Louis Pradel Hospital, Cardiovascular Functional Explorations Service and CIC of Lyon, Lyon, France.&#xD;INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, INRA U1235, INSA of Lyon, Rockefeller and Charles Merieux Lyon-Sud Medical Universities, Lyon, France Hospices Civils de Lyon, Lyon-Sud Hospital, Endocrinology, Diabetology, and Nutrition Service, Pierre-Benite, France.</auth-address><titles><title>Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>3279-94</pages><volume>63</volume><number>10</number><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Cells, Cultured</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Hepatocytes/cytology/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Intracellular Membranes/*metabolism</keyword><keyword>Liver/*metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mitochondria/*metabolism</keyword><keyword>Signal Transduction/physiology</keyword></keywords><dates><year>2014</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1939-327X (Electronic)&#xD;0012-1797 (Linking)</isbn><accession-num>24947355</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24947355</url></related-urls></urls><electronic-resource-num>10.2337/db13-1751</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Shinjo</Author><Year>2017</Year><RecNum>678</RecNum><DisplayText>[546, 547]</DisplayText><record><rec-number>678</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">678</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shinjo, S.</author><author>Jiang, S.</author><author>Nameta, M.</author><author>Suzuki, T.</author><author>Kanai, M.</author><author>Nomura, Y.</author><author>Goda, N.</author></authors></contributors><auth-address>Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan; Research Institute for Life Support Innovation, Research Organization for Nano &amp; Life Innovation, Waseda University, Tokyo 162-0041, Japan. Electronic address: stshinjo@gmail.com.&#xD;Niigata College of Medical Technology, Niigata 950-2076, Japan.&#xD;Department of Electron Microscope Core Facility, Niigata University, Niigata 951-8510, Japan.&#xD;Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.&#xD;Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan; School of Creative Science and Engineering, Waseda University, Tokyo 162-8480, Japan.</auth-address><titles><title>Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid-induced insulin resistance</title><secondary-title>Exp Cell Res</secondary-title><alt-title>Experimental cell research</alt-title></titles><periodical><full-title>Exp Cell Res</full-title><abbr-1>Experimental cell research</abbr-1></periodical><alt-periodical><full-title>Exp Cell Res</full-title><abbr-1>Experimental cell research</abbr-1></alt-periodical><pages>86-93</pages><volume>359</volume><number>1</number><keywords><keyword>Endoplasmic Reticulum/drug effects/*metabolism</keyword><keyword>Endoplasmic Reticulum Stress/drug effects</keyword><keyword>Hep G2 Cells</keyword><keyword>Humans</keyword><keyword>Insulin/pharmacology</keyword><keyword>*Insulin Resistance</keyword><keyword>Intracellular Membranes/drug effects/*metabolism</keyword><keyword>Membrane Proteins/metabolism</keyword><keyword>Mitochondria/drug effects/*metabolism</keyword><keyword>Mitochondrial Proteins/metabolism</keyword><keyword>Palmitic Acid/*pharmacology</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Proto-Oncogene Proteins c-akt/metabolism</keyword><keyword>Reactive Oxygen Species/metabolism</keyword><keyword>Signal Transduction/drug effects</keyword><keyword>eIF-2 Kinase/metabolism</keyword></keywords><dates><year>2017</year><pub-dates><date>Oct 1</date></pub-dates></dates><isbn>1090-2422 (Electronic)&#xD;0014-4827 (Linking)</isbn><accession-num>28827061</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28827061</url></related-urls></urls><electronic-resource-num>10.1016/j.yexcr.2017.08.006</electronic-resource-num></record></Cite><Cite><Author>Tubbs</Author><Year>2014</Year><RecNum>679</RecNum><record><rec-number>679</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">679</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tubbs, E.</author><author>Theurey, P.</author><author>Vial, G.</author><author>Bendridi, N.</author><author>Bravard, A.</author><author>Chauvin, M. A.</author><author>Ji-Cao, J.</author><author>Zoulim, F.</author><author>Bartosch, B.</author><author>Ovize, M.</author><author>Vidal, H.</author><author>Rieusset, J.</author></authors></contributors><auth-address>INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, INRA U1235, INSA of Lyon, Rockefeller and Charles Merieux Lyon-Sud Medical Universities, Lyon, France.&#xD;INSERM UMR-1052, Cancer Research Center of Lyon, Lyon 1 University, Hospices Civils de Lyon, Lyon, France.&#xD;INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, INRA U1235, INSA of Lyon, Rockefeller and Charles Merieux Lyon-Sud Medical Universities, Lyon, France Hospices Civils de Lyon, Louis Pradel Hospital, Cardiovascular Functional Explorations Service and CIC of Lyon, Lyon, France.&#xD;INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, INRA U1235, INSA of Lyon, Rockefeller and Charles Merieux Lyon-Sud Medical Universities, Lyon, France Hospices Civils de Lyon, Lyon-Sud Hospital, Endocrinology, Diabetology, and Nutrition Service, Pierre-Benite, France.</auth-address><titles><title>Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance</title><secondary-title>Diabetes</secondary-title><alt-title>Diabetes</alt-title></titles><periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></periodical><alt-periodical><full-title>Diabetes</full-title><abbr-1>Diabetes</abbr-1></alt-periodical><pages>3279-94</pages><volume>63</volume><number>10</number><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Cells, Cultured</keyword><keyword>Endoplasmic Reticulum/*metabolism</keyword><keyword>Hepatocytes/cytology/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin/*metabolism</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Intracellular Membranes/*metabolism</keyword><keyword>Liver/*metabolism</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mitochondria/*metabolism</keyword><keyword>Signal Transduction/physiology</keyword></keywords><dates><year>2014</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1939-327X (Electronic)&#xD;0012-1797 (Linking)</isbn><accession-num>24947355</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24947355</url></related-urls></urls><electronic-resource-num>10.2337/db13-1751</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE.DATA 546, 547. Further, growing literature suggests that over activation of mitochondria due to obesity and enhanced insulin secretion leads to inhibition of AMPK activity. The importance of targeting AMPK for mitochondrial diseases and its involvement in metabolic reprograming has been recently reviewed by We et al 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 548. Indeed several small molecules like metformin that inhibits mitochondrial activity are known to enhance AMPK-dependent insulin sensitivity. Having noticed that PHLPP1 has direct impact on ER stress induction, AMPK activity as well as it can alter mitochondrial potentiality, it will be interesting to assess whether PHLPP1 has any direct regulation on intracellular calcium signaling as well as maintaining the functional integrity of MAM and its interdependence on AMPK activity for cellular homeostasis in insulin sensitive tissues. Although underlying molecular imprints for transcriptional up-regulation of PHLPP1 during ER stress are yet to be studied, Matinspector based analysis of the upstream region of PHLPP1 (~ 1.5 kb) gene showed the presence of potential binding sites for ER stress transducers such as ATF4 and sXBP1 which are conserved across mouse, rat and humans 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 549.PHLPP1 regulates glucose uptake: PHLPP1 is known to impair insulin-stimulated glucose uptake by direct inactivation of Akt 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 459. In our present study, we revealed an additional mechanism of PHLPP1-dependent Akt inhibition through up-regulation of the pseudo-kinase Trb3. Trb3 is a direct binder of Akt that blocks its activation through unknown process thereby impairing insulin-stimulated glucose uptake 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 87. Ablation of PHLPP1 expression in mice improved the rate of glucose clearance from the circulation along with enhanced Akt phosphorylation and reduced tunicamycin-induced Trb3 expression. Considering the influence of PHPP1 on whole body glucose clearance, we explored the impact of PHLPP1 on GLUT4 activity. GLUT4 is the key glucose transporter; its expression is depleted in the skeletal muscle of mice fed on lipid-rich diet 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 550. Consistently, our lab also reported that chronic exposure to pro-inflammatory cytokines induces PIMT/HDAC5 mediated GLUT4 transcriptional repression 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 470. Further, treatment of mouse myotubes with chemical ER chaperones like 4-PABA enhanced GLUT4 transcript abundance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 512. The protein levels of GLUT4 were depleted in a dose-dependent manner, with a parallel increase in HDAC5 protein levels upon over-expression of PHLPP1. Conversely, depletion of PHLPP1 in mouse myotubes precluded tunicamycin stimulated HDAC5 enhancement and GLUT4 depletion indicating that PHLPP1 regulates HDAC5 / GLUT4axis in part through the induction of ER stress. PHLPP1 regulates the cellular activity of AMPK:Here, we noted that PHLPP1 1) augments ER stress, 2) inhibits insulin-stimulated glucose uptake and 3) regulates GLUT4/HDAC5 and thus GLUT4 transcription 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 511. Additionally, we also noted an increase in basal glucose uptake in PHLPP1 depleted cells, an insulin-independent glucose uptake phenomenon. Hence, in search of a target of PHLPP1 in the insulin-independent pathway, we identified AMPK, a master regulator of energy metabolism, to be directly dephosphorylated by PHLPP1. AMPK regulates insulin-independent glucose uptake by suppressing AS160 activity (short term) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 509, 551 and enhancing GLUT4 levels (longer duration) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 511. Further, TNF-? and ER stress were reported to mediate skeletal muscle insulin resistance through the inhibition of AMPK activity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 57, 337. Importantly, activation of AMPK via chemical inducers or exercise restrained ER stress thereby improving insulin-sensitivity and whole body glucose metabolism 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 552, 553. Upon activation of AMPK by chemical inducers like AICAR and A769662, PHLPP1 induced ER stress response was observed to be curbed, indicating that PHLPP1 may facilitate ER stress via the inhibition of AMPK activity. Thus, PHLPP1 may function as a key mediator of ER stress-induced IR by unplugging both insulin-induced Akt signaling as well as insulin independent AMPK activity.Although several phosphatases of AMPK are reported in cultured cells and in vitro 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 554, 555, the identification of relevant phosphatase(s) of AMPK in vivo remained obscure, especially in the skeletal muscle. Here, we observed that the association of PHLPP1 but not PP2Ac or PP2C? with AMPK? was enhanced in ER-stressed myoblasts and soleus muscle of HFD fed mice. However, PP2C? proposed in TNF-? induced AMPK inhibition and skeletal muscle insulin resistance 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 57, failed to precipitate with AMPK both in cultured cells and skeletal muscle of HFD mice, suggesting an indirect inhibition of AMPK by PP2C?. Based on our observations, we speculate that PHLPP1 may be relevant in vivo phosphatase of AMPK in skeletal muscle under pathological conditions of ER stress and IR. However, in our data, we have not explored any possible post-translation modification(s) that may enhance the inherent catalytic activity of PP2A without influencing its interaction with AMPK. But considering the complexity of different heterotrimers of PP2A across different tissues 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 489, targeting PHLPP1 with small molecules for improving insulin sensitivity seems to be therapeutically more practical. Since all the reported kinase/protein of PHLPP family substrates are regulated by both PHLPP1 and PHLPP2, it will be interesting to assess the possibility of PHLPP2 dephosphorylating AMPK.Although PHLPP isoforms are categorized as unique PP2C phosphatases, certain key differences between the catalytic activity of PP2C? and PHLPP exist. For instance, under in vitro conditions, PHLPP isoforms are active in the absence of divalent metal ion, but PP2C? requires either Mg2+ or Mn2+ for its activity 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 363. We speculate that the efficacy in the in vitro potency of PHLPP1 and PP2C? towards AMPK? could be a result of these differences in their competence towards their substrates. As reported by Dr. Newton and colleagues, the activity of PP2C? shows ~2-3folds higher activity towards model substrate pNPP and synthetic peptides than bacterially purified PP2C domains of PHLPP1 and PHLPP2 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 363. These differences in the efficiency of PHLPP isoforms and PP2C? towards their substrates could be due to either intrinsic differences in their catalytic activity or due to missing of un-identified co-factor/allosteric regulator(s) of PHLPP isoforms.ERK1/2 phosphorylates PHLPP1upon ER stress:ER stress activates the three known canonical MAPKs viz: ERK1/2, JNK, and p38 with different kinetics resulting in varied cellular responses 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 556, 557. JNK and p38 are known hamper the insulin signalling by phosphorylating IRS at Ser307, directly or indirectly 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 558, 559, while emerging data from various studies implicate the role of ERK activity in the development of IR <EndNote><Cite><Author>Ozaki</Author><Year>2016</Year><RecNum>484</RecNum><DisplayText>[470, 518, 560]</DisplayText><record><rec-number>484</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">484</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozaki, K. I.</author><author>Awazu, M.</author><author>Tamiya, M.</author><author>Iwasaki, Y.</author><author>Harada, A.</author><author>Kugisaki, S.</author><author>Tanimura, S.</author><author>Kohno, M.</author></authors></contributors><auth-address>Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; and.&#xD;Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.&#xD;Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; and kohnom@nagasaki-u.ac.jp.</auth-address><titles><title>Targeting the ERK signaling pathway as a potential treatment for insulin resistance and type 2 diabetes</title><secondary-title>Am J Physiol Endocrinol Metab</secondary-title><alt-title>American journal of physiology. Endocrinology and metabolism</alt-title></titles><periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></alt-periodical><pages>E643-E651</pages><volume>310</volume><number>8</number><dates><year>2016</year><pub-dates><date>Apr 15</date></pub-dates></dates><isbn>1522-1555 (Electronic)&#xD;0193-1849 (Linking)</isbn><accession-num>26860984</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/26860984</url></related-urls></urls><electronic-resource-num>10.1152/ajpendo.00445.2015</electronic-resource-num></record></Cite><Cite><Author>Kain</Author><Year>2015</Year><RecNum>9</RecNum><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611488">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kain, V.</author><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Seshadri, S.</author><author>Prajapati, B.</author><author>Jena, P. K.</author><author>Teja Meda, C. L.</author><author>Subramanian, M.</author><author>Kaimal Suraj, S.</author><author>Kumar, S. T.</author><author>Prakash Babu, P.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Parsa, K. V.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr. Reddy&apos;s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.&#xD;Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>Co-activator binding protein PIMT mediates TNF-alpha induced insulin resistance in skeletal muscle via the transcriptional down-regulation of MEF2A and GLUT4</title><secondary-title>Sci Rep</secondary-title></titles><periodical><full-title>Sci Rep</full-title></periodical><pages>15197</pages><volume>5</volume><edition>2015/10/16</edition><keywords><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Cells, Cultured</keyword><keyword>Down-Regulation/drug effects</keyword><keyword>Glucose Transporter Type 4/genetics/*metabolism</keyword><keyword>HEK293 Cells</keyword><keyword>Histone Deacetylases/genetics/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin Resistance</keyword><keyword>MEF2 Transcription Factors/genetics/metabolism</keyword><keyword>Male</keyword><keyword>Mitogen-Activated Protein Kinase 1/metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 3/metabolism</keyword><keyword>Myoblasts, Skeletal/cytology/metabolism</keyword><keyword>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Transcription Factors/genetics/metabolism</keyword><keyword>Transcription, Genetic/*drug effects</keyword><keyword>Tumor Necrosis Factor-alpha/blood/*pharmacology</keyword></keywords><dates><year>2015</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>2045-2322 (Electronic)&#xD;2045-2322 (Linking)</isbn><accession-num>26468734</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26468734</url></related-urls></urls><custom2>PMC4606566</custom2><electronic-resource-num>10.1038/srep15197</electronic-resource-num></record></Cite><Cite><Author>Kapadia</Author><Year>2013</Year><RecNum>8</RecNum><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611456">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Parsa, K. V.</author><author>Kain, V.</author><author>Behera, S.</author><author>Suraj, S. K.</author><author>Babu, P. P.</author><author>Kar, A.</author><author>Panda, S.</author><author>Zhu, Y. J.</author><author>Jia, Y.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr Reddy&apos;s Institute of Life Sciences, An Associate Institute of University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Life Sciences, Devi Ahilya University, Indore, Madhya Pradesh, India.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>ERK2-mediated phosphorylation of transcriptional coactivator binding protein PIMT/NCoA6IP at Ser298 augments hepatic gluconeogenesis</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e83787</pages><volume>8</volume><number>12</number><edition>2013/12/21</edition><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Female</keyword><keyword>Gene Expression Regulation/drug effects</keyword><keyword>Gluconeogenesis/drug effects/*physiology</keyword><keyword>Glucose/biosynthesis</keyword><keyword>Hepatocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Liver/*metabolism</keyword><keyword>MAP Kinase Signaling System/drug effects</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mitogen-Activated Protein Kinase 1/*metabolism</keyword><keyword>Models, Biological</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>Protein Binding</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/genetics</keyword><keyword>Rats</keyword><keyword>Substrate Specificity</keyword><keyword>Thyroid Hormones/pharmacology</keyword><keyword>Transcription, Genetic</keyword><keyword>Transcriptional Activation</keyword></keywords><dates><year>2013</year></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>24358311</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/24358311</url></related-urls></urls><custom2>PMC3866170</custom2><electronic-resource-num>10.1371/journal.pone.0083787</electronic-resource-num></record></Cite></EndNote> ADDIN EN.CITE <EndNote><Cite><Author>Ozaki</Author><Year>2016</Year><RecNum>484</RecNum><DisplayText>[470, 518, 560]</DisplayText><record><rec-number>484</rec-number><foreign-keys><key app="EN" db-id="pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav">484</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ozaki, K. I.</author><author>Awazu, M.</author><author>Tamiya, M.</author><author>Iwasaki, Y.</author><author>Harada, A.</author><author>Kugisaki, S.</author><author>Tanimura, S.</author><author>Kohno, M.</author></authors></contributors><auth-address>Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; and.&#xD;Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.&#xD;Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; and kohnom@nagasaki-u.ac.jp.</auth-address><titles><title>Targeting the ERK signaling pathway as a potential treatment for insulin resistance and type 2 diabetes</title><secondary-title>Am J Physiol Endocrinol Metab</secondary-title><alt-title>American journal of physiology. Endocrinology and metabolism</alt-title></titles><periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></alt-periodical><pages>E643-E651</pages><volume>310</volume><number>8</number><dates><year>2016</year><pub-dates><date>Apr 15</date></pub-dates></dates><isbn>1522-1555 (Electronic)&#xD;0193-1849 (Linking)</isbn><accession-num>26860984</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/26860984</url></related-urls></urls><electronic-resource-num>10.1152/ajpendo.00445.2015</electronic-resource-num></record></Cite><Cite><Author>Kain</Author><Year>2015</Year><RecNum>9</RecNum><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611488">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kain, V.</author><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Seshadri, S.</author><author>Prajapati, B.</author><author>Jena, P. K.</author><author>Teja Meda, C. L.</author><author>Subramanian, M.</author><author>Kaimal Suraj, S.</author><author>Kumar, S. T.</author><author>Prakash Babu, P.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Parsa, K. V.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr. Reddy&apos;s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.&#xD;Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>Co-activator binding protein PIMT mediates TNF-alpha induced insulin resistance in skeletal muscle via the transcriptional down-regulation of MEF2A and GLUT4</title><secondary-title>Sci Rep</secondary-title></titles><periodical><full-title>Sci Rep</full-title></periodical><pages>15197</pages><volume>5</volume><edition>2015/10/16</edition><keywords><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Cells, Cultured</keyword><keyword>Down-Regulation/drug effects</keyword><keyword>Glucose Transporter Type 4/genetics/*metabolism</keyword><keyword>HEK293 Cells</keyword><keyword>Histone Deacetylases/genetics/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin Resistance</keyword><keyword>MEF2 Transcription Factors/genetics/metabolism</keyword><keyword>Male</keyword><keyword>Mitogen-Activated Protein Kinase 1/metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 3/metabolism</keyword><keyword>Myoblasts, Skeletal/cytology/metabolism</keyword><keyword>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Transcription Factors/genetics/metabolism</keyword><keyword>Transcription, Genetic/*drug effects</keyword><keyword>Tumor Necrosis Factor-alpha/blood/*pharmacology</keyword></keywords><dates><year>2015</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>2045-2322 (Electronic)&#xD;2045-2322 (Linking)</isbn><accession-num>26468734</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26468734</url></related-urls></urls><custom2>PMC4606566</custom2><electronic-resource-num>10.1038/srep15197</electronic-resource-num></record></Cite><Cite><Author>Kapadia</Author><Year>2013</Year><RecNum>8</RecNum><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611456">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Parsa, K. 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In numerous cancerous cells, ER stress-induced ERK1/2 activation depends partially on the activation of IRE1 and up-regulation of BiP expression 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 561, 562. Treatment of diabetic mice like ob/ob or KKAy mice with ERK inhibitors like PD184352 showed significant improvement in glucose clearance from the circulation ADDIN EN.CITE <EndNote><Cite><Author>Ozaki</Author><Year>2016</Year><RecNum>484</RecNum><DisplayText>560</DisplayText><record><rec-number>484</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>484</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ozaki, K. I.</author><author>Awazu, M.</author><author>Tamiya, M.</author><author>Iwasaki, Y.</author><author>Harada, A.</author><author>Kugisaki, S.</author><author>Tanimura, S.</author><author>Kohno, M.</author></authors></contributors><auth-address>Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; and. Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan. Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; and [email protected].</auth-address><titles><title>Targeting the ERK signaling pathway as a potential treatment for insulin resistance and type 2 diabetes</title><secondary-title>Am J Physiol Endocrinol Metab</secondary-title><alt-title>American journal of physiology. Endocrinology and metabolism</alt-title></titles><periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Endocrinol Metab</full-title><abbr-1>American journal of physiology. Endocrinology and metabolism</abbr-1></alt-periodical><pages>E643-E651</pages><volume>310</volume><number>8</number><dates><year>2016</year><pub-dates><date>Apr 15</date></pub-dates></dates><isbn>1522-1555 (Electronic) 0193-1849 (Linking)</isbn><accession-num>26860984</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/26860984</url></related-urls></urls><electronic-resource-num>10.1152/ajpendo.00445.2015</electronic-resource-num></record></Cite></EndNote>560. Recently, Hwang et al. reported that ER stress suppresses skeletal muscle insulin sensitivity through an inhibitory cross-talk between ERK1/2 and AMPK 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ADDIN EN.CITE.DATA 337. Genetic or pharmacological inhibition of ERK1/2 led to enhanced phosphorylation of AMPK; however, the underlying mechanisms were unknown. Supporting the possibility of widespread involvement of ERK1/2 in insulin resistance, we have recently published that ERK1/2 induces skeletal muscle insulin resistance through the phosphorylation of a co-activator binding protein, PIMT <EndNote><Cite><Author>Kain</Author><Year>2015</Year><RecNum>9</RecNum><DisplayText>[470, 518]</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611488">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kain, V.</author><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Seshadri, S.</author><author>Prajapati, B.</author><author>Jena, P. K.</author><author>Teja Meda, C. L.</author><author>Subramanian, M.</author><author>Kaimal Suraj, S.</author><author>Kumar, S. T.</author><author>Prakash Babu, P.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Parsa, K. V.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr. Reddy&apos;s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.&#xD;Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>Co-activator binding protein PIMT mediates TNF-alpha induced insulin resistance in skeletal muscle via the transcriptional down-regulation of MEF2A and GLUT4</title><secondary-title>Sci Rep</secondary-title></titles><periodical><full-title>Sci Rep</full-title></periodical><pages>15197</pages><volume>5</volume><edition>2015/10/16</edition><keywords><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Cells, Cultured</keyword><keyword>Down-Regulation/drug effects</keyword><keyword>Glucose Transporter Type 4/genetics/*metabolism</keyword><keyword>HEK293 Cells</keyword><keyword>Histone Deacetylases/genetics/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin Resistance</keyword><keyword>MEF2 Transcription Factors/genetics/metabolism</keyword><keyword>Male</keyword><keyword>Mitogen-Activated Protein Kinase 1/metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 3/metabolism</keyword><keyword>Myoblasts, Skeletal/cytology/metabolism</keyword><keyword>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Transcription Factors/genetics/metabolism</keyword><keyword>Transcription, Genetic/*drug effects</keyword><keyword>Tumor Necrosis Factor-alpha/blood/*pharmacology</keyword></keywords><dates><year>2015</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>2045-2322 (Electronic)&#xD;2045-2322 (Linking)</isbn><accession-num>26468734</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26468734</url></related-urls></urls><custom2>PMC4606566</custom2><electronic-resource-num>10.1038/srep15197</electronic-resource-num></record></Cite><Cite><Author>Kapadia</Author><Year>2013</Year><RecNum>8</RecNum><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611456">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Parsa, K. V.</author><author>Kain, V.</author><author>Behera, S.</author><author>Suraj, S. K.</author><author>Babu, P. P.</author><author>Kar, A.</author><author>Panda, S.</author><author>Zhu, Y. J.</author><author>Jia, Y.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr Reddy&apos;s Institute of Life Sciences, An Associate Institute of University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Life Sciences, Devi Ahilya University, Indore, Madhya Pradesh, India.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>ERK2-mediated phosphorylation of transcriptional coactivator binding protein PIMT/NCoA6IP at Ser298 augments hepatic gluconeogenesis</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e83787</pages><volume>8</volume><number>12</number><edition>2013/12/21</edition><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Female</keyword><keyword>Gene Expression Regulation/drug effects</keyword><keyword>Gluconeogenesis/drug effects/*physiology</keyword><keyword>Glucose/biosynthesis</keyword><keyword>Hepatocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Liver/*metabolism</keyword><keyword>MAP Kinase Signaling System/drug effects</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mitogen-Activated Protein Kinase 1/*metabolism</keyword><keyword>Models, Biological</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>Protein Binding</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/genetics</keyword><keyword>Rats</keyword><keyword>Substrate Specificity</keyword><keyword>Thyroid Hormones/pharmacology</keyword><keyword>Transcription, Genetic</keyword><keyword>Transcriptional Activation</keyword></keywords><dates><year>2013</year></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>24358311</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/24358311</url></related-urls></urls><custom2>PMC3866170</custom2><electronic-resource-num>10.1371/journal.pone.0083787</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Kain</Author><Year>2015</Year><RecNum>9</RecNum><DisplayText>[470, 518]</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611488">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kain, V.</author><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Seshadri, S.</author><author>Prajapati, B.</author><author>Jena, P. K.</author><author>Teja Meda, C. L.</author><author>Subramanian, M.</author><author>Kaimal Suraj, S.</author><author>Kumar, S. T.</author><author>Prakash Babu, P.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Parsa, K. V.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr. Reddy&apos;s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.&#xD;Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>Co-activator binding protein PIMT mediates TNF-alpha induced insulin resistance in skeletal muscle via the transcriptional down-regulation of MEF2A and GLUT4</title><secondary-title>Sci Rep</secondary-title></titles><periodical><full-title>Sci Rep</full-title></periodical><pages>15197</pages><volume>5</volume><edition>2015/10/16</edition><keywords><keyword>Animals</keyword><keyword>Blood Glucose/analysis</keyword><keyword>Cells, Cultured</keyword><keyword>Down-Regulation/drug effects</keyword><keyword>Glucose Transporter Type 4/genetics/*metabolism</keyword><keyword>HEK293 Cells</keyword><keyword>Histone Deacetylases/genetics/metabolism</keyword><keyword>Humans</keyword><keyword>Insulin Resistance</keyword><keyword>MEF2 Transcription Factors/genetics/metabolism</keyword><keyword>Male</keyword><keyword>Mitogen-Activated Protein Kinase 1/metabolism</keyword><keyword>Mitogen-Activated Protein Kinase 3/metabolism</keyword><keyword>Myoblasts, Skeletal/cytology/metabolism</keyword><keyword>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Wistar</keyword><keyword>Transcription Factors/genetics/metabolism</keyword><keyword>Transcription, Genetic/*drug effects</keyword><keyword>Tumor Necrosis Factor-alpha/blood/*pharmacology</keyword></keywords><dates><year>2015</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>2045-2322 (Electronic)&#xD;2045-2322 (Linking)</isbn><accession-num>26468734</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/26468734</url></related-urls></urls><custom2>PMC4606566</custom2><electronic-resource-num>10.1038/srep15197</electronic-resource-num></record></Cite><Cite><Author>Kapadia</Author><Year>2013</Year><RecNum>8</RecNum><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="ff0rxapwfpdfstepfv6pwrftz0ewfepfepsv" timestamp="1520611456">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kapadia, B.</author><author>Viswakarma, N.</author><author>Parsa, K. V.</author><author>Kain, V.</author><author>Behera, S.</author><author>Suraj, S. K.</author><author>Babu, P. P.</author><author>Kar, A.</author><author>Panda, S.</author><author>Zhu, Y. J.</author><author>Jia, Y.</author><author>Thimmapaya, B.</author><author>Reddy, J. K.</author><author>Misra, P.</author></authors></contributors><auth-address>Department of Biology, Dr Reddy&apos;s Institute of Life Sciences, An Associate Institute of University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, Andhra Pradesh, India.&#xD;Department of Life Sciences, Devi Ahilya University, Indore, Madhya Pradesh, India.&#xD;Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.&#xD;Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.</auth-address><titles><title>ERK2-mediated phosphorylation of transcriptional coactivator binding protein PIMT/NCoA6IP at Ser298 augments hepatic gluconeogenesis</title><secondary-title>PLoS One</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e83787</pages><volume>8</volume><number>12</number><edition>2013/12/21</edition><keywords><keyword>Animals</keyword><keyword>Cell Line</keyword><keyword>Female</keyword><keyword>Gene Expression Regulation/drug effects</keyword><keyword>Gluconeogenesis/drug effects/*physiology</keyword><keyword>Glucose/biosynthesis</keyword><keyword>Hepatocytes/*metabolism</keyword><keyword>Humans</keyword><keyword>Liver/*metabolism</keyword><keyword>MAP Kinase Signaling System/drug effects</keyword><keyword>Mice</keyword><keyword>Mice, Knockout</keyword><keyword>Mitogen-Activated Protein Kinase 1/*metabolism</keyword><keyword>Models, Biological</keyword><keyword>Phosphorylation/drug effects</keyword><keyword>Promoter Regions, Genetic</keyword><keyword>Protein Binding</keyword><keyword>Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics/*metabolism</keyword><keyword>Protein-Serine-Threonine Kinases/genetics</keyword><keyword>Rats</keyword><keyword>Substrate Specificity</keyword><keyword>Thyroid Hormones/pharmacology</keyword><keyword>Transcription, Genetic</keyword><keyword>Transcriptional Activation</keyword></keywords><dates><year>2013</year></dates><isbn>1932-6203 (Electronic)&#xD;1932-6203 (Linking)</isbn><accession-num>24358311</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/24358311</url></related-urls></urls><custom2>PMC3866170</custom2><electronic-resource-num>10.1371/journal.pone.0083787</electronic-resource-num></record></Cite></EndNote>  ADDIN EN.CITE.DATA 470, 518. Further, we have also shown recently that PHLPP1 controls ERK1/2 activation in a context-specific manner ADDIN EN.CITE <EndNote><Cite><Author>Alamuru</Author><Year>2014</Year><RecNum>71</RecNum><DisplayText>371</DisplayText><record><rec-number>71</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>71</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Alamuru, N. P.</author><author>Behera, S.</author><author>Butchar, J. P.</author><author>Tridandapani, S.</author><author>Kaimal Suraj, S.</author><author>Babu, P. P.</author><author>Hasnain, S. E.</author><author>Ehtesham, N. Z.</author><author>Parsa, K. V.</author></authors></contributors><auth-address>Dr. Reddy's Institute of Life Sciences (DRILS), Hyderabad, India. Department of Biotechnology, University of Hyderabad, Hyderabad, India. Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA. Department of Biological Sciences, Indian Institute of Technology, New Delhi, India; and. National Institute of Pathology, Safdarjung Hospital, New Delhi, India. Dr. Reddy's Institute of Life Sciences (DRILS), Hyderabad, India; [email protected].</auth-address><titles><title>A novel immunomodulatory function of PHLPP1: inhibition of iNOS via attenuation of STAT1 ser727 phosphorylation in mouse macrophages</title><secondary-title>J Leukoc Biol</secondary-title><alt-title>Journal of leukocyte biology</alt-title></titles><periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></periodical><alt-periodical><full-title>J Leukoc Biol</full-title><abbr-1>Journal of leukocyte biology</abbr-1></alt-periodical><pages>775-783</pages><volume>95</volume><number>5</number><dates><year>2014</year><pub-dates><date>May</date></pub-dates></dates><isbn>1938-3673 (Electronic) 0741-5400 (Linking)</isbn><accession-num>24443556</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/24443556</url></related-urls></urls><electronic-resource-num>10.1189/jlb.0713360</electronic-resource-num></record></Cite></EndNote>371. Supporting the above findings conceptually and using a systematic approach of computational analysis, in vitro and cellular studies supported by multiple biochemical tools, we identified here that PHLPP1 to be phosphorylated by ERK1/2 at Ser932 target site both in vitro and in vivo. Phosphorylation of PHLPP1 augments its cellular functionality: Post-translational modifications (PTMs) enable a fast reversible regulation of protein functionality. Regulation of enzyme (kinases and phosphatases) by PTMs is known to modulate their enzyme activity and substrate interactions. Interestingly, very limited information is publically available regarding phospho-modification of the PHLPP1 phosphatase that can influence its catalytic activity. Zhang et al. described the association of Tyr phosphorylation of PHLPP1 with its enhanced activity upon insulin stimulation 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ADDIN EN.CITE.DATA 428, however, failed to provide the mechanism in physiological/pathological context. In this study, we presented the evidence that the phosphorylation of PHLPP1? at Ser932 was enhanced in tunicamycin-treated ER-stressed cells and was required for its ability to inactivate AMPK and Akt. Thus, our study projected PHLPP1 as one of the missing links between Erk1/2 and AMPK inactivation during cellular response to ER stress. We identified in this study that the phosphorylation of Ser932 augmented the phosphatase activity of PHLPP1?. Phosphorylated PHLPP1 (PHLPP1 co-transfection with Raf-BXB) showed enhanced activity in vitro than basally phosphorylated PHLPP1 (in absence of Raf-BXB). Consistently, the ability of PHLPP1? to dephosphorylate AMPK in vitro was dampened upon mutation of Ser932 to Ala (phospho-deficient) mutation. However, the dephosphorylating activity of phospho-mimic mutant (Ser932Asp) of PHLPP1? towards AMPK was almost comparable to that of the wild-type. In agreement with our in vitro data, phospho-deficient PHLPP1? lost its ability to remove the inorganic phosphate moiety from Thr172 of AMPK and Ser473 of Akt in intact cells. Further, the association of PHLPP1? with its substrates (Akt and AMPK) was also enhanced upon induction of ER stress in Ser932 phosphorylation-dependent manner. Important to note that phospho-mimic mutation strengthened the basal interaction of PHLPP1? with AMPK and Akt and failed to further enhance the interaction in the presence of tunicamycin-induced ER stress, indicating that presence of negative charge plays an important role in strengthening the interaction with its substrates. The dynamic nature of this regulation can be further appreciated by the observation that PHLPP1?-AMPK complex formation was dissociated upon AICAR or A769662 treatment with minimal effects on the PHLPP1?-Akt association. Such modulation in the interaction between AMPK with PHLPP1? is probably due to the conformational change in AMPK that would preclude the access to PHLPP1?. Consistent with the interaction experiments, we observed that the ability of PHLPP1? to induce ER stress and insulin resistance was reduced due to phospho-deficient mutation while the phospho-mimic mutant of PHLPP1? was functionally equivalent to the wild type. Apart from enzymatic activity, post-translational modification of the protein can alter the protein’s stability as well as its localization. However, the PHLPP1 stability, as well as its localization, was observed to be independent of its phosphorylation status. Based on these observations, we speculate that addition of negative charge at Ser932 residue of PHLPP1? may likely bring about a conformational change in the phosphatase that may aid in its interaction with its substrates and thereby potentially enhance its catalytic activity towards its substrates. Although we showed that Ser932 phosphorylation of PHLPP1? is required for its activity both in vitro and in intact cells, it remains to be firmly established whether Ser932 phosphorylation sustains the catalytic activity of PHLPP1? by enhancing intrinsic phosphatase activity or strengthening the interaction with its substrates or both. A complete landscape of the differential interacting protein partners of PHLPP1 in the presence and absence of phosphorylation will provide a comprehensive view about the emerging substrates as well as the unidentified co-factors/allosteric modulators of its activity. Summary of work: Collectively, PHLPP1 acts by at least three independent routes, although interlinked, to control skeletal muscle insulin sensitivity. 1) Being identified as Akt dephosphorylating enzyme, enhanced activity of PHLPP1 hampers insulin-stimulated glucose uptake either by direct dephosphorylation of Akt and/or via TRB3 mediated inhibition 2) Regulatory feedback activation between PHLPP1 and ER stress also plays an eminent role in diminishing the insulin signalling cascade 3) Here, we identified that PHLPP1 interacts and dephosphorylates AMPK that inhibits insulin-independent glucose uptake. This study raises the possibility that pharmacological inhibition of PHLPP1 could provide a useful therapeutic approach for combating the effects of ER stress in progression to diabetes. A recent finding has been reported using chemical PHLPP inhibitors NSC45586 and NSC117079 in the treatment of joint injury in animal models 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 453. Exploring such inhibitors may be providing certain fruitful information in designing therapeutics for the treatment of insulin resistance associated diseases. Limitations and future work: The current study was first of its kind in delineating the molecular imprints of PHLPP1 impact on insulin sensitivity in skeletal muscle. Here we reported that PHLPP1 augments ER stress by inhibiting AMPK activity. Also, PHLPP limits GLUT4 transcript in part via HDAC5 upregulation. However, more detailed investigations are necessary to further delineate the comprehensive role of PHLPP1 in insulin resistance. Herein, we noted that PHLPP1 transcript levels were enhanced upon ER stress in skeletal muscle. However, the transcription factor(s) that activate PHLPP1 promoter activity in response to ER stress is still elusive. We in another study have observed a Sp1 mediated regulation of PHLPP1 promoter activity in bacterial endotoxin treated mouse macrophages 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 389. Hence, it will be interesting to see whether PHLPP1 promoter activity is regulated by Sp1 in tunicamycin/ thapsigargin-treated cells as well. Further Matinspector analysis displayed numerous ER stress-induced transcription factor binding sites. Thus, a molecular detailed analysis is needed to be performed at the PHLPP1 promoter in presence/absence of chemical ER stress inducers along with physiological context to delineate PHLPP1 transcriptional regulation.It is also possible that increase in the PHLPP1 transcript levels is independent of its transcriptional regulation and regulated by miRNA driven post-transcriptional regulation. As described in section 1.7.3, there are numerous miRNA reported that target PHLPP1 3’UTR altering the mRNA stability and thus controlling PHLPP1 translation. Maurel and Chevet have compiled a panel of miRNA that are known to alter the ER stress response ADDIN EN.CITE <EndNote><Cite><Author>Maurel</Author><Year>2013</Year><RecNum>481</RecNum><DisplayText>563</DisplayText><record><rec-number>481</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>481</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Maurel, M.</author><author>Chevet, E.</author></authors></contributors><auth-address>INSERM U1053, Bordeaux, France. [email protected]</auth-address><titles><title>Endoplasmic reticulum stress signaling: the microRNA connection</title><secondary-title>Am J Physiol Cell Physiol</secondary-title><alt-title>American journal of physiology. Cell physiology</alt-title></titles><periodical><full-title>Am J Physiol Cell Physiol</full-title><abbr-1>American journal of physiology. Cell physiology</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Cell Physiol</full-title><abbr-1>American journal of physiology. Cell physiology</abbr-1></alt-periodical><pages>C1117-26</pages><volume>304</volume><number>12</number><keywords><keyword>Animals</keyword><keyword>Endoplasmic Reticulum Stress/*genetics</keyword><keyword>Homeostasis/genetics</keyword><keyword>Humans</keyword><keyword>MicroRNAs/*genetics</keyword><keyword>Signal Transduction/*genetics</keyword><keyword>Unfolded Protein Response/genetics/*physiology</keyword></keywords><dates><year>2013</year><pub-dates><date>Jun 15</date></pub-dates></dates><isbn>1522-1563 (Electronic) 0363-6143 (Linking)</isbn><accession-num>23515532</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23515532</url></related-urls></urls><electronic-resource-num>10.1152/ajpcell.00061.2013</electronic-resource-num></record></Cite></EndNote>563. It will be interesting to see whether any of the reported or unidentified miRNA in UPR response signals can play a role in regulating the PHLPP1 transcript levels. Indeed preliminary scanning of the potential miRNA targeting PHLPP1 3’UTR using Target scan, revealed that miRNA-199a-5p (which hampers BiP expression in prostate, colon and human cancer cell lines) 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 564 can alter PHLPP1 expression. It was earlier shown that miRNA-199a-5p targets PHLPP1 to promote cetuximab drug resistance in colon cancer cells 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 565. However, it will be interesting to test whether miR-199a-5p has any impact on PHLPP1 expression, ER stress and insulin sensitivity in skeletal muscle. Another limitation of the current work is in context of PHLPP1 and GLUT4 transcript. Here we reported that PHLPP1 depletes GLUT4 levels along with a parallel increase in HDAC5 protein level in a dose-dependent manner. It is well documented that high fat fed rodents in skeletal muscle reduce GLUT4 transcript, while high sucrose diet induces HDAC5 translocation and thus hampers GLUT4 promoter activity. In our study, we noted that GLUT4 protein levels were reduced upon overexpression of PHLPP1. It will be interesting to assess whether the decrease in GLUT4 protein is due to the reduction in the transcript or some other post-translation mechanism. Also, we noted that PHLPP1 induce the expression of the HDAC5 protein. In one of our earlier study, we have reported that TGS1/PIMT under the influence TNF-? activated ERK enhances HDAC5 promoter activity 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ADDIN EN.CITE.DATA 470. Thus it will be interesting to study if there is any cross-talk between PHLPP1 andTGS1 pathways in the control of-HDAC5/GLUT4 levels. The current study was pursed in skeletal muscle, the prime site for glucose uptake. In recent years, accumulating evidence from clinical and rodents based studies uncovered the existence of insulin resistance within the hypothalamus ADDIN EN.CITE <EndNote><Cite><Author>Chen</Author><Year>2017</Year><RecNum>684</RecNum><DisplayText>566</DisplayText><record><rec-number>684</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>684</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Chen, W.</author><author>Balland, E.</author><author>Cowley, M. A.</author></authors></contributors><auth-address>Department of Physiology/Biomedical Discovery Institute, Monash University, Clayton, VIC, Australia.</auth-address><titles><title>Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis</title><secondary-title>Neuroendocrinology</secondary-title><alt-title>Neuroendocrinology</alt-title></titles><periodical><full-title>Neuroendocrinology</full-title><abbr-1>Neuroendocrinology</abbr-1></periodical><alt-periodical><full-title>Neuroendocrinology</full-title><abbr-1>Neuroendocrinology</abbr-1></alt-periodical><pages>364-381</pages><volume>104</volume><number>4</number><keywords><keyword>Animals</keyword><keyword>Diabetes Mellitus, Type 2/*metabolism/*physiopathology</keyword><keyword>Glucose/*metabolism</keyword><keyword>Homeostasis/*physiology</keyword><keyword>Humans</keyword><keyword>Hypothalamus/*metabolism</keyword><keyword>Insulin Resistance/*physiology</keyword><keyword>Leptin/physiology</keyword><keyword>Obesity/*metabolism/*physiopathology</keyword><keyword>Signal Transduction/physiology</keyword></keywords><dates><year>2017</year></dates><isbn>1423-0194 (Electronic) 0028-3835 (Linking)</isbn><accession-num>28122381</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/28122381</url></related-urls></urls><electronic-resource-num>10.1159/000455865</electronic-resource-num></record></Cite></EndNote>566. To date, it is still elusive whether hyperinsulinemia causes insulin resistance, which underlies the pathogenesis of obesity-associated type 2 diabetes, due to the complex regulatory network, which prevails in the periphery and in the brain. Growing evidence supports the premise that reduced central nervous system insulin signalling from either defective secretion or action contributes to the pathogenesis of metabolic disorders and may therefore help to explain the close association between these two disorders. Indeed, using Drosophila as the model organism, Zhang et al proposed that hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity 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ADDIN EN.CITE.DATA 567. A number of studies have established that PHLPP1 plays a vital role in learning and memory formation 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 369. Also emerging data suggest that hypothalamic AMPK (a substrate of PHLPP1) activity may act as master regulator of energy homeostasis 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ADDIN EN.CITE 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ADDIN EN.CITE.DATA 568. Hence, it is tempting to dissect the functional importance of hypothalamic PHLPP1 expression/activity in regulating the whole body energy homeostasis.PHLPP family comprises two isozymes PHLPP1 and PHLPP2, while PHLPP1 has two splice variants PHLP1? and PHLPP1?. The current study was performed using PHLPP1? for the overexpression as well as the in vitro study. Since most of the substrate reported in the literature for PHLPP1 is common for all the isoform, it will be interesting to check whether PHLPP2 and PHLPP1? will have any impact of AMPK activity. Also, different isoforms of PHLPP1 displays a different affinity for Akt isoform. Thus it will be interesting to examine the effect on PHLPP isoforms on different complexes of AMPK. A recent study established that PHLPP2 (but not PHLPP1) degradation induces lipogenesis without effecting gluconeogenesis in obese mice as patients with non-alcoholic fatty liver disease (NAFLD) 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ADDIN EN.CITE.DATA 423. Conversely, ectopic expression of PHLPP2 in hepatocytes improved the insulin sensitivity by inhibiting lipid accumulation. Also miRNAs like miR-27a and miR181a that are known to regulate CHOP, TRB3, ATF4 and ATF3 expression ADDIN EN.CITE <EndNote><Cite><Author>Maurel</Author><Year>2013</Year><RecNum>481</RecNum><DisplayText>563</DisplayText><record><rec-number>481</rec-number><foreign-keys><key app=”EN” db-id=”pdtsaved7ppwr0e0s2qvz2zf0wxrx2xd0aav”>481</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Maurel, M.</author><author>Chevet, E.</author></authors></contributors><auth-address>INSERM U1053, Bordeaux, France. [email protected]</auth-address><titles><title>Endoplasmic reticulum stress signaling: the microRNA connection</title><secondary-title>Am J Physiol Cell Physiol</secondary-title><alt-title>American journal of physiology. Cell physiology</alt-title></titles><periodical><full-title>Am J Physiol Cell Physiol</full-title><abbr-1>American journal of physiology. Cell physiology</abbr-1></periodical><alt-periodical><full-title>Am J Physiol Cell Physiol</full-title><abbr-1>American journal of physiology. Cell physiology</abbr-1></alt-periodical><pages>C1117-26</pages><volume>304</volume><number>12</number><keywords><keyword>Animals</keyword><keyword>Endoplasmic Reticulum Stress/*genetics</keyword><keyword>Homeostasis/genetics</keyword><keyword>Humans</keyword><keyword>MicroRNAs/*genetics</keyword><keyword>Signal Transduction/*genetics</keyword><keyword>Unfolded Protein Response/genetics/*physiology</keyword></keywords><dates><year>2013</year><pub-dates><date>Jun 15</date></pub-dates></dates><isbn>1522-1563 (Electronic) 0363-6143 (Linking)</isbn><accession-num>23515532</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/pubmed/23515532</url></related-urls></urls><electronic-resource-num>10.1152/ajpcell.00061.2013</electronic-resource-num></record></Cite></EndNote>563 (established ER stress markers) also target PHLPP2 3’UTR 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ADDIN EN.CITE 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