Featured Publications
BRD7 improves glucose homeostasis independent of IRS proteins.
Kim Y, Lee J, Han Y, Tao R, White M, Liu R, Park S. BRD7 improves glucose homeostasis independent of IRS proteins. Journal Of Endocrinology 2023, 258 PMID: 37578842, PMCID: PMC10430774, DOI: 10.1530/joe-23-0119.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGlucoseHomeostasisInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLiverMiceMice, KnockoutMice, ObeseObesityReceptor, InsulinTranscription FactorsConceptsGlucose homeostasisKnockout miceAlternative insulinObese miceGlucose homeostasis independentGlucose metabolism parametersContext of obesityBlood glucose levelsMetabolism parametersGlucose levelsGlucose metabolismInsulinMiceIRS proteinsInsulin receptorProtein 7ObesityHomeostasisUpregulationBRD7InvolvementPathwayNovel insightsEuglycemiaFindingsThe P300 acetyltransferase inhibitor C646 promotes membrane translocation of insulin receptor protein substrate and interaction with the insulin receptor
Peng J, Ramatchandirin B, Wang Y, Pearah A, Namachivayam K, Wolf R, Steele K, MohanKumar K, Yu L, Guo S, White M, Maheshwari A, He L. The P300 acetyltransferase inhibitor C646 promotes membrane translocation of insulin receptor protein substrate and interaction with the insulin receptor. Journal Of Biological Chemistry 2022, 298: 101621. PMID: 35074429, PMCID: PMC8850660, DOI: 10.1016/j.jbc.2022.101621.Peer-Reviewed Original ResearchMeSH KeywordsBenzoatesEnzyme InhibitorsHumansInsulinInsulin Receptor Substrate ProteinsNitrobenzenesP300-CBP Transcription FactorsPhosphorylationPyrazolonesReceptor, InsulinTyrosineConceptsAbsence of insulinP300 acetyltransferase activityTyrosine kinase activityAcetyltransferase activityInsulin receptorObese patientsTyrosine phosphorylationRole of acetylationInsulinNormal functionMembrane translocationSubsequent activationC646PatientsLiver hepatocytesProtein substratesInhibitionReceptorsMolecular mechanismsHepatocytesPhosphorylationBeta subunitKinase activityObesityUnique effects
2021
Irs2 deficiency alters hippocampus-associated behaviors during young adulthood
Tanokashira D, Wang W, Maruyama M, Kuroiwa C, White M, Taguchi A. Irs2 deficiency alters hippocampus-associated behaviors during young adulthood. Biochemical And Biophysical Research Communications 2021, 559: 148-154. PMID: 33940386, PMCID: PMC8361845, DOI: 10.1016/j.bbrc.2021.04.101.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody Temperature RegulationDiabetes Mellitus, Type 2Energy MetabolismGene DeletionHippocampusInsulin Receptor Substrate ProteinsMaleMiceMice, Inbred C57BLConceptsYoung adult male miceAdult male miceMale miceAlzheimer's diseaseType 2 diabetes mellitusInsulin-like growth factor-1Brain energy metabolismGrowth factor-1Young adult malesCore body temperatureDiabetes mellitusInsulin resistanceInsulin/insulin-like growth factor-1Risk factorsBehavioral alterationsCognitive impairmentGenetic backgroundPremature deathHippocampusMiceYoung adulthoodAberrant alterationsFactor 1Abnormal changesBody temperatureFoxO1 suppresses Fgf21 during hepatic insulin resistance to impair peripheral glucose utilization and acute cold tolerance
Stöhr O, Tao R, Miao J, Copps K, White M. FoxO1 suppresses Fgf21 during hepatic insulin resistance to impair peripheral glucose utilization and acute cold tolerance. Cell Reports 2021, 34: 108893. PMID: 33761350, PMCID: PMC8529953, DOI: 10.1016/j.celrep.2021.108893.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAdipocytes, BrownAdipose Tissue, BrownAnimalsBlood GlucoseBody WeightCold TemperatureDiet, High-FatFibroblast Growth FactorsForkhead Box Protein O1Gene Expression RegulationGlucoseHomeostasisInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLipid MetabolismLiverMice, KnockoutOrgan SpecificityOxidation-ReductionThermogenesisConceptsHepatic insulin resistanceInsulin resistanceGlucose utilizationHigher plasma Fgf21 levelsSevere hepatic insulin resistanceFGF21 knockout micePlasma FGF21 levelsPeripheral glucose utilizationInsulin-resistant miceThermogenic gene expressionFGF21 resistancePharmacologic formsFGF21 levelsCold intoleranceFGF21 functionMetabolic healthBAT functionGlucose homeostasisKnockout miceFGF21Adenoviral infectionMiceWeight lossSkeletal muscleAcute cold toleranceInsulin receptor substrate 1, but not IRS2, plays a dominant role in regulating pancreatic alpha cell function in mice
Takatani T, Shirakawa J, Shibue K, Gupta M, Kim H, Lu S, Hu J, White M, Kennedy R, Kulkarni R. Insulin receptor substrate 1, but not IRS2, plays a dominant role in regulating pancreatic alpha cell function in mice. Journal Of Biological Chemistry 2021, 296: 100646. PMID: 33839150, PMCID: PMC8131928, DOI: 10.1016/j.jbc.2021.100646.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGlucagonGlucagon-Secreting CellsGlucose IntoleranceInsulin Receptor Substrate ProteinsInsulin ResistanceMaleMiceMice, KnockoutPhosphorylationSignal TransductionConceptsAKT Ser/Thr kinaseInsulin receptor substrate (IRS) proteinsSer/Thr kinaseAlpha-cell functionGlobal protein translationCell functionInsulin receptor substrate-1Pancreatic alpha-cell functionDownstream target genesReceptor substrate-1Alpha cellsAlpha-cell lineGlucagon secretionSubstrate proteinsProtein translationTarget genesSubstrate-1Downstream proteinsDominant regulatorPancreatic alpha cellsMitochondrial dysfunctionCognate receptorsIRS2Normal glucose toleranceCell lines
2020
Paraventricular, subparaventricular and periventricular hypothalamic IRS4-expressing neurons are required for normal energy balance
Sutton A, Gonzalez I, Sadagurski M, Rajala M, Lu C, Allison M, Adams J, Myers M, White M, Olson D. Paraventricular, subparaventricular and periventricular hypothalamic IRS4-expressing neurons are required for normal energy balance. Scientific Reports 2020, 10: 5546. PMID: 32218485, PMCID: PMC7099088, DOI: 10.1038/s41598-020-62468-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnergy MetabolismFemaleGene Knockdown TechniquesInsulin Receptor Substrate ProteinsMaleMiceNeuronsNitric Oxide Synthase Type IObesityParaventricular Hypothalamic NucleusReceptors, OxytocinConceptsEnergy expenditureEnergy expenditure regulationAnti-obesity therapiesFeeding-related behaviorsNormal energy balanceInsulin receptor substrate 4Negative energy balancePVH neuronsHypothalamic circuitryHypothalamic sitesEnergy balance controlFeeding suppressionParaventricular nucleusSatiety responseSubstantial obesityNormal feedingPVHNeuronsViral toolsNeural componentsHindbrain regionsObesityRequisite roleBalance controlEnergy balanceInsulin receptor substrates differentially exacerbate insulin-mediated left ventricular remodeling
Riehle C, Weatherford E, Wende A, Jaishy B, Seei A, McCarty N, Rech M, Shi Q, Reddy G, Kutschke W, Oliveira K, Pires K, Anderson J, Diakos N, Weiss R, White M, Drakos S, Xiang Y, Abel E. Insulin receptor substrates differentially exacerbate insulin-mediated left ventricular remodeling. JCI Insight 2020, 5: e134920. PMID: 32213702, PMCID: PMC7213803, DOI: 10.1172/jci.insight.134920.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiomegalyHumansHyperinsulinismInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceMiceMice, KnockoutProto-Oncogene Proteins c-aktVentricular RemodelingConceptsTransverse aortic constrictionInsulin receptor substrate-1Left ventricular remodelingHeart failureVentricular remodelingCardiac hypertrophyTAC-induced LV hypertrophyPressure-overload cardiac hypertrophySevere LV dysfunctionInsulin receptor tyrosine kinase activityAkt1 activationReceptor tyrosine kinase activityLV dysfunctionLV hypertrophyWT miceInsulin resistanceLV remodelingAortic constrictionProinflammatory responseProtein kinase GInsulin receptor substrateReceptor substrate-1Kinomic profilingWT controlsTyrosine kinase activity
2018
Hyperglycemia induces vascular smooth muscle cell dedifferentiation by suppressing insulin receptor substrate-1–mediated p53/KLF4 complex stabilization
Xi G, Shen X, Wai C, White M, Clemmons D. Hyperglycemia induces vascular smooth muscle cell dedifferentiation by suppressing insulin receptor substrate-1–mediated p53/KLF4 complex stabilization. Journal Of Biological Chemistry 2018, 294: 2407-2421. PMID: 30578299, PMCID: PMC6378959, DOI: 10.1074/jbc.ra118.005398.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCell DifferentiationHumansHyperglycemiaInsulin Receptor Substrate ProteinsInsulin ResistanceKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMice, KnockoutMultiprotein ComplexesMuscle, Smooth, VascularMyocytes, Smooth MuscleProtein StabilityProto-Oncogene MasProto-Oncogene Proteins c-mdm2SwineTumor Suppressor Protein p53ConceptsKrüppel-like factor 4Vascular smooth muscle cell dedifferentiationSmooth muscle cell dedifferentiationInsulin receptor substrate-1Muscle cell dedifferentiationNormoglycemic miceAtherosclerotic lesionsHigh glucoseVSMC differentiationInsulin resistance stateP53 levelsIRS-1 knockdownSmooth muscle protein 22P53 associationExpression of p21Cell dedifferentiationMarker protein expressionAccelerates AtherosclerosisNondiabetic pigsDiabetic pigsIRS-1 overexpressionNutlin-3 treatmentMDM2/p53Receptor substrate-1MDM2 proto-oncogeneAblation of insulin receptor substrates 1 and 2 suppresses Kras-driven lung tumorigenesis
Xu H, Lee M, Tsai P, Adler A, Curry N, Challa S, Freinkman E, Hitchcock D, Copps K, White M, Bronson R, Marcotrigiano M, Wu Y, Clish C, Kalaany N. Ablation of insulin receptor substrates 1 and 2 suppresses Kras-driven lung tumorigenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 4228-4233. PMID: 29610318, PMCID: PMC5910837, DOI: 10.1073/pnas.1718414115.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAmino AcidsAnimalsAutophagyCarcinogenesisCarcinoma, Non-Small-Cell LungCodon, TerminatorGenes, rasHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor ILung NeoplasmsMiceNeoplasm ProteinsProteolysisProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)Signal TransductionConceptsIR/IGF1RLung cancerLung tumorigenesisInsulin receptorTumor cellsInsulin-like growth factor 1 receptorCell lung cancerGrowth factor 1 receptorHuman NSCLC cellsEffective therapeutic strategyLung cancer initiationIntracellular levelsKirsten rat sarcomaFactor 1 receptorTumor burdenCancer deathLeading causeMutant NSCLCNSCLC cellsIGF1R inhibitionMouse modelTherapeutic strategiesInsulin/IGF1Acute lossRat sarcoma
2016
Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation*
Xi G, Wai C, White M, Clemmons D. Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation*. Journal Of Biological Chemistry 2016, 292: 2009-2020. PMID: 28003360, PMCID: PMC5290970, DOI: 10.1074/jbc.m116.758987.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DedifferentiationDown-RegulationHumansHyperglycemiaInsulin Receptor Substrate ProteinsKruppel-Like Factor 4MiceMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleReceptors, ImmunologicConceptsInsulin receptor substrate-1Receptor substrate-1IRS-1Differentiated stateSubstrate-1Aberrant signalingMetabolic stressVascular smooth muscle cell dedifferentiationIGF-I stimulationIRS-1 expressionVascular smooth muscle cell migrationScaffold proteinSHPS-1Transcription factorsSmooth muscle cell dedifferentiationSmooth muscle cell migrationMuscle cell dedifferentiationMuscle cell migrationReceptor signalsVSMC dedifferentiationCell migrationInsulin-like growth factor ICell dedifferentiationMajor risk factorDevelopment of atherosclerosisG protein-coupled receptors (GPCRs) That Signal via Protein Kinase A (PKA) Cross-talk at Insulin Receptor Substrate 1 (IRS1) to Activate the phosphatidylinositol 3-kinase (PI3K)/AKT Pathway*
Law N, White M, Hunzicker-Dunn M. G protein-coupled receptors (GPCRs) That Signal via Protein Kinase A (PKA) Cross-talk at Insulin Receptor Substrate 1 (IRS1) to Activate the phosphatidylinositol 3-kinase (PI3K)/AKT Pathway*. Journal Of Biological Chemistry 2016, 291: 27160-27169. PMID: 27856640, PMCID: PMC5207145, DOI: 10.1074/jbc.m116.763235.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCells, CulturedCyclic AMP-Dependent Protein KinasesFemaleGranulosa CellsHumansInsulin Receptor Substrate ProteinsOvarian FolliclePhosphatidylinositol 3-KinasePhosphorylationProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledSignal TransductionThyroid NeoplasmsConceptsG protein-coupled receptorsInsulin receptor substrate-1PI3K/Akt cascadeProtein-coupled receptorsAkt cascadeSer/ThrReceptor substrate-1PI3K/Akt activationInsulin-like growth factor-1PI3K/Akt pathwayGranulosa cellsConserved mechanismPI3K/AktCellular functionsProtein kinaseSer residuesSubstrate-1Myosin phosphataseSubunit 1Akt activationCell survivalAutocrine/paracrine mannerViral oncoproteinsAkt pathwayPreantral granulosa cellsIRS proteins and diabetic complications
Lavin D, White M, Brazil D. IRS proteins and diabetic complications. Diabetologia 2016, 59: 2280-2291. PMID: 27514532, PMCID: PMC5506098, DOI: 10.1007/s00125-016-4072-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes ComplicationsDiabetes Mellitus, Type 2FemaleHumansInsulin Receptor Substrate ProteinsMaleMiceSignal TransductionConceptsIRS proteinsType 2 diabetesDiabetic complicationsMitogen-activated protein kinaseElicit cellular responsesCoronary artery diseaseElevated blood glucoseComplications of diabetesProtein kinaseDownstream effectorsAdaptor moleculeInsulin signalingCellular responsesNumber of organsInsulin receptorMacrovascular complicationsMicrovascular complicationsArtery diseasePatient morbidityBlood glucoseProteinMale micePatient outcomesCell proliferationComplicationsInsulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma
Metz H, Kargl J, Busch S, Kim K, Kurland B, Abberbock S, Randolph-Habecker J, Knoblaugh S, Kolls J, White M, Houghton A. Insulin receptor substrate-1 deficiency drives a proinflammatory phenotype in KRAS mutant lung adenocarcinoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8795-8800. PMID: 27439864, PMCID: PMC4978299, DOI: 10.1073/pnas.1601989113.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate-1Janus kinase/signal transducerKinase/signal transducerTumor burdenActivator of transcriptionReceptor substrate-1IRS-1 deficiencyKRAS-mutant lung adenocarcinomaInsulin-like growth factor receptorAdenoviral Cre recombinaseIL-22 receptorMutant lung adenocarcinomaTumor-promoting inflammationAdaptor proteinSignificant survival disadvantageGrowth factor receptorSignal transducerSubstrate-1PI3KProinflammatory phenotypeLung cancerLung adenocarcinomaMutant subgroupTissue microarrayCre recombinaseSerine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase*
Copps K, Hançer N, Qiu W, White M. Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase*. Journal Of Biological Chemistry 2016, 291: 8602-8617. PMID: 26846849, PMCID: PMC4861431, DOI: 10.1074/jbc.m116.714915.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsCHO CellsCricetinaeCricetulusGene DeletionGlucose IntoleranceInsulinInsulin Receptor Substrate ProteinsLiverMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicMultiprotein ComplexesMutation, MissensePhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktRibosomal Protein S6 KinasesSerineSignal TransductionTOR Serine-Threonine KinasesTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsConceptsInsulin receptor substrate-1Receptor substrate-1PI3K associationS6 kinaseSubstrate-1Insulin-stimulated Akt activityAkt phosphorylationK associationRapamycin complex 1S6K signalingInsulin-stimulated IRS1 tyrosine phosphorylationSer-302IRS1 tyrosine phosphorylationMTORC1 inhibitor rapamycinRibosomal S6 proteinTsc1 deletionFeedback phosphorylationIntracellular amino acidsInsulin sensitivityTyrosine phosphorylationAlanine mutationsS6 proteinS6KAkt activityInsulin signaling
2014
IRS2 integrates insulin/IGF1 signalling with metabolism, neurodegeneration and longevity
White M. IRS2 integrates insulin/IGF1 signalling with metabolism, neurodegeneration and longevity. Diabetes Obesity And Metabolism 2014, 16: 4-15. PMID: 25200290, DOI: 10.1111/dom.12347.Peer-Reviewed Original ResearchConceptsInsulin/IGF1Central nervous systemInsulin-like signalingLife spanOrganisms showsCellular functionsNutrient homeostasisInsulin resistanceGenetic manipulationSystemic insulin resistanceClinical Alzheimer's diseaseType 2 diabetesEnergy homeostasisNeurodegenerative diseasesMetabolismNeurodegenerationCompensatory hyperinsulinaemiaHomeostasisProgressive neurodegenerationSystemic metabolismIGF1Excess insulinNervous systemAlzheimer's diseaseClinical perspectiveInsulin Receptor Substrates Are Essential for the Bioenergetic and Hypertrophic Response of the Heart to Exercise Training
Riehle C, Wende A, Zhu Y, Oliveira K, Pereira R, Jaishy B, Bevins J, Valdez S, Noh J, Kim B, Moreira A, Weatherford E, Manivel R, Rawlings T, Rech M, White M, Abel E. Insulin Receptor Substrates Are Essential for the Bioenergetic and Hypertrophic Response of the Heart to Exercise Training. Molecular And Cellular Biology 2014, 34: 3450-3460. PMID: 25002528, PMCID: PMC4135616, DOI: 10.1128/mcb.00426-14.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEnergy MetabolismGene Expression RegulationGlycogenHeartInsulin Receptor Substrate ProteinsMiceMice, Inbred C57BLMice, KnockoutMitochondriaPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPhosphatidylinositol 3-KinasesProtein IsoformsSignal TransductionSwimmingTranscription FactorsConceptsInsulin receptor substrate-1IRS isoformsProtein phosphatase 2AReceptor substrate-1Insulin receptor substrateInsulin-like growth factor 1 receptorGrowth factor 1 receptorSynthase kinase-3βPeroxisome proliferator-activated receptor gamma coactivatorPhosphatase 2AProliferator-activated receptor gamma coactivatorFactor 1 receptorPGC-1α protein contentCardiomyocyte-specific deletionDevelopmental regulationProtein contentHypertrophic responseReceptor substrateReceptor gamma coactivatorFatty acid oxidationSubstrate-1Kinase-3βDivergent rolesMetabolic adaptationNonredundant roleAPPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of IRS1/2 to the Insulin Receptor
Ryu J, Galan A, Xin X, Dong F, Abdul-Ghani M, Zhou L, Wang C, Li C, Holmes B, Sloane L, Austad S, Guo S, Musi N, DeFronzo R, Deng C, White M, Liu F, Dong L. APPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of IRS1/2 to the Insulin Receptor. Cell Reports 2014, 7: 1227-1238. PMID: 24813896, PMCID: PMC4380268, DOI: 10.1016/j.celrep.2014.04.006.Peer-Reviewed Original ResearchInsulin and Metabolic Stress Stimulate Multisite Serine/Threonine Phosphorylation of Insulin Receptor Substrate 1 and Inhibit Tyrosine Phosphorylation*
Hançer N, Qiu W, Cherella C, Li Y, Copps K, White M. Insulin and Metabolic Stress Stimulate Multisite Serine/Threonine Phosphorylation of Insulin Receptor Substrate 1 and Inhibit Tyrosine Phosphorylation*. Journal Of Biological Chemistry 2014, 289: 12467-12484. PMID: 24652289, PMCID: PMC4007441, DOI: 10.1074/jbc.m114.554162.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnisomycinAntigens, CDBlotting, WesternCHO CellsCricetinaeCricetulusEnzyme InhibitorsHumansHypoglycemic AgentsInsulinInsulin Receptor Substrate ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktRatsReceptor, InsulinRibosomal Protein S6 Kinases, 70-kDaSerineSignal TransductionThapsigarginThreonineTOR Serine-Threonine KinasesTunicamycinTyrosineConceptsTyrosine phosphorylationPhospho-specific monoclonal antibodiesSerine/threonine phosphorylationInsulin receptor tyrosine kinasePI3KInsulin receptor substrate-1Insulin-stimulated cellsHuman insulin receptorIRS1 tyrosine phosphorylationReceptor substrate-1Metabolic stressReceptor tyrosine kinasesThreonine phosphorylationThreonine residuesS6 kinasePI3K inhibitionSubstrate-1Mechanistic targetTyrosine kinaseInsulin stimulationMEK pathwayKey substrateInsulin receptorPresence of inhibitorsCHO cells
2013
IRS1Ser307 phosphorylation does not mediate mTORC1-induced insulin resistance
Herrema H, Lee J, Zhou Y, Copps K, White M, Ozcan U. IRS1Ser307 phosphorylation does not mediate mTORC1-induced insulin resistance. Biochemical And Biophysical Research Communications 2013, 443: 689-693. PMID: 24333417, PMCID: PMC3926104, DOI: 10.1016/j.bbrc.2013.12.023.Peer-Reviewed Original ResearchConceptsInsulin resistanceGlucose intoleranceInsulin sensitivityImpaired insulin receptorStress-induced insulin resistanceRapamycin complex 1 (mTORC1) activityPhosphorylation of IRS1Endoplasmic reticulum stressDiabetic miceER stress-induced insulin resistanceMammalian targetIRS1 phosphorylationReticulum stressMiceIntoleranceInsulin receptorVivoSer307Insulin receptor substrate signaling suppresses neonatal autophagy in the heart
Riehle C, Wende A, Sena S, Pires K, Pereira R, Zhu Y, Bugger H, Frank D, Bevins J, Chen D, Perry C, Dong X, Valdez S, Rech M, Sheng X, Weimer B, Gottlieb R, White M, Abel E. Insulin receptor substrate signaling suppresses neonatal autophagy in the heart. Journal Of Clinical Investigation 2013, 123: 5319-5333. PMID: 24177427, PMCID: PMC3859408, DOI: 10.1172/jci71171.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAnimalsApoptosisApoptosis Regulatory ProteinsAutophagyBeclin-1Cardiomyopathy, DilatedFetal HeartHeartHeart FailureInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IMiceMitochondria, HeartMyocytes, CardiacOxidative PhosphorylationPhosphorylationProtein Processing, Post-TranslationalReceptor, IGF Type 1Signal TransductionTOR Serine-Threonine KinasesConceptsInsulin receptor substrateInduction of autophagyActivation of mTORIGF-1R signalingPostnatal cardiac developmentUnrestrained autophagyCardiomyocyte-specific deletionGenetic suppressionCardiac developmentReceptor substrateIGF-1 receptorEssential adaptationProsurvival signalingAutophagic fluxAutophagy suppressionAutophagyMitochondrial dysfunctionMammalian heartPhysiological suppressionNeonatal starvationAutophagic activationSignalingIRS1IRS2Insulin action