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 ResearchConceptsGlucose 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 ResearchConceptsAbsence of insulinP300 acetyltransferase activityTyrosine kinase activityAcetyltransferase activityInsulin receptorObese patientsTyrosine phosphorylationRole of acetylationInsulinNormal functionMembrane translocationSubsequent activationC646PatientsLiver hepatocytesProtein substratesInhibitionReceptorsMolecular mechanismsHepatocytesPhosphorylationBeta subunitKinase activityObesityUnique effects
2021
Insulin action at a molecular level – 100 years of progress
White M, Kahn C. Insulin action at a molecular level – 100 years of progress. Molecular Metabolism 2021, 52: 101304. PMID: 34274528, PMCID: PMC8551477, DOI: 10.1016/j.molmet.2021.101304.Peer-Reviewed Original ResearchConceptsAmino acid sequenceType 2 diabetesFunction of insulinAcid sequenceMolecular knowledgeHuman diseasesInsulin-sensitive tissuesPhysiological functionsPhysiological roleInsulin receptorInsulin-resistant statesInsulin 100 yearsInsulin actionBlood glucoseCascadeInsulinDiabetesTissueDiscoveryRegulationTreatmentRemarkable advancesRoleSequenceYears
2013
Direct Autocrine Action of Insulin on β-Cells: Does It Make Physiological Sense?
Rhodes C, White M, Leahy J, Kahn S. Direct Autocrine Action of Insulin on β-Cells: Does It Make Physiological Sense? Diabetes 2013, 62: 2157-2163. PMID: 23801714, PMCID: PMC3712043, DOI: 10.2337/db13-0246.Peer-Reviewed Original ResearchConceptsΒ-cellsDirect autocrine effectsTransgenic mouse studiesSignal transductionPancreatic β-cellsDownstream elementsAutocrine actionRelevant ligandsΒ-cell functionAutocrine effectsMouse studiesCircumstantial evidencePhysiological senseTransductionAvailable experimental evidencePathwayInsightsExperimental evidenceInsulin
2012
IRS2 Signaling in LepR-b Neurons Suppresses FoxO1 to Control Energy Balance Independently of Leptin Action
Sadagurski M, Leshan R, Patterson C, Rozzo A, Kuznetsova A, Skorupski J, Jones J, Depinho R, Myers M, White M. IRS2 Signaling in LepR-b Neurons Suppresses FoxO1 to Control Energy Balance Independently of Leptin Action. Cell Metabolism 2012, 15: 703-712. PMID: 22560222, PMCID: PMC3361909, DOI: 10.1016/j.cmet.2012.04.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCytoskeletal ProteinsEnergy MetabolismFemaleForkhead Box Protein O1Forkhead Transcription FactorsGene ExpressionGlucoseGlucose IntoleranceHomeostasisInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLeptinMaleMiceMice, TransgenicNerve Tissue ProteinsNeuronsObesityReceptors, LeptinSignal TransductionConceptsLeptin actionGlucose homeostasisGlucose intoleranceInsulin resistanceHormone leptinFoxO1 nuclear exclusionIRS2 expressionLeptin receptorMetabolic actionsNeuronsMiceEnergy balanceFOXO1Metabolic sensingIRS2HomeostasisGene expressionNuclear exclusionObesityLeptinExpressionCNSInsulinIntoleranceBrainThe AKTion in non-canonical insulin signaling
Cheng Z, White M. The AKTion in non-canonical insulin signaling. Nature Medicine 2012, 18: 351-353. PMID: 22395698, PMCID: PMC3982803, DOI: 10.1038/nm.2694.Peer-Reviewed Original Research
2009
The IRS2 Gly1057Asp Variant Is Associated With Human Longevity
Barbieri M, Rizzo M, Papa M, Boccardi V, Esposito A, White M, Paolisso G. The IRS2 Gly1057Asp Variant Is Associated With Human Longevity. The Journals Of Gerontology Series A 2009, 65A: 282-286. PMID: 19887537, DOI: 10.1093/gerona/glp154.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate 2Gene polymorphismsYears of ageIGF-1 signalingSs-cell functionInsulin-like growth factor-1 signalingIrs2 branchInsulin resistanceInsulin sensitivityMetabolic covariatesGly1057Asp variantIRS2 geneExtreme old ageLarge population groupsInternal medicineC participantsOlder ageHuman longevityCommon polymorphismsIGF signalingInsulinFurther studiesPopulation groupsAgeWhole population
2008
Insulin-Like Signaling, Nutrient Homeostasis, and Life Span
Taguchi A, White M. Insulin-Like Signaling, Nutrient Homeostasis, and Life Span. Annual Review Of Physiology 2008, 70: 191-212. PMID: 17988211, DOI: 10.1146/annurev.physiol.70.113006.100533.Peer-Reviewed Original Research
2006
Regulating insulin signaling and -cell function through IRS proteinsThis paper is one of a selection of papers published in this Special Issue, entitled Second Messengers and Phosphoproteins12th International Conference.
White M. Regulating insulin signaling and -cell function through IRS proteinsThis paper is one of a selection of papers published in this Special Issue, entitled Second Messengers and Phosphoproteins12th International Conference. Canadian Journal Of Physiology And Pharmacology 2006, 84: 725-737. PMID: 16998536, DOI: 10.1139/y06-008.Peer-Reviewed Original ResearchConceptsType 2 diabetesInsulin resistanceBeta-cell destructionPeripheral insulin resistanceDiabetes mellitusChronic hyperglycemiaSystemic disordersFemale infertilityInsulin secretionCardiovascular diseaseCell functionInevitable progressionComplex disorderDisordersDiabetesGreater frequencyPrevalent formInsulinPhosphoproteins12th International ConferenceAgeSecond messengerDyslipidemiaHypertensionMellitusAutoimmune
2004
Islet-Sparing Effects of Protein Tyrosine Phosphatase-1b Deficiency Delays Onset of Diabetes in IRS2 Knockout Mice
Kushner J, Haj F, Klaman L, Dow M, Kahn B, Neel B, White M. Islet-Sparing Effects of Protein Tyrosine Phosphatase-1b Deficiency Delays Onset of Diabetes in IRS2 Knockout Mice. Diabetes 2004, 53: 61-66. PMID: 14693698, DOI: 10.2337/diabetes.53.1.61.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseCrosses, GeneticDiabetes Mellitus, Type 1Glucose Tolerance TestInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansKineticsLeptinMaleMiceMice, KnockoutModels, AnimalPhosphoproteinsProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine PhosphatasesSignal TransductionConceptsPeripheral insulin sensitivityBeta-cell areaBeta-cell functionInsulin sensitivityPancreatic beta cell areaPancreatic beta-cell functionDecreased insulin requirementIrs2 knockout miceBeta cell homeostasisMonths of ageInsulin requirementsPeripheral actionsGlucose toleranceGlucose homeostasisKnockout miceDelay onsetMiceInsulin receptorPTP1B deficiencyDiabetesReceptor complexIRS2Novel roleInsulinDownstream targets
2003
Insulin Signaling in Health and Disease
White M. Insulin Signaling in Health and Disease. Science 2003, 302: 1710-1711. PMID: 14657487, DOI: 10.1126/science.1092952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesDiabetes MellitusDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2HumansInflammationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansMiceModels, BiologicalObesityPhosphoproteinsPhosphorylationReceptor, InsulinSignal TransductionSomatomedins
2002
The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth
Kitamura T, Nakae J, Kitamura Y, Kido Y, Biggs W, Wright C, White M, Arden K, Accili D. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth. Journal Of Clinical Investigation 2002, 110: 1839-1847. PMID: 12488434, PMCID: PMC151657, DOI: 10.1172/jci16857.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell NucleusDiabetes Mellitus, Type 2Epithelial CellsForkhead Box Protein O1Forkhead Transcription FactorsGenes, ReporterHomeodomain ProteinsHumansInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansKidneyMiceMice, KnockoutMicroscopy, FluorescencePancreasPhosphoproteinsPromoter Regions, GeneticProtein IsoformsReceptor, InsulinSignal TransductionTrans-ActivatorsTranscription FactorsConceptsBeta-cell failureBeta-cell proliferationBeta cellsInsulin-producing beta cellsBeta-cell massCell proliferationInsulin receptor substrate 2Pdx1 expressionPancreatic β-cell growthΒ-cell growthTranscription factor FOXO1Pancreatic ductSubset of cellsForkhead transcription factor FOXO1Cell failureNuclear expressionInsulin/IGFRelative deficiencyMutant FoxO1Pdx1 promoterProgenitor cellsFOXO1Gene 1InsulinMiceInsulin Signaling After Exercise in Insulin Receptor Substrate-2-Deficient Mice
Howlett K, Sakamoto K, Hirshman M, Aschenbach W, Dow M, White M, Goodyear L. Insulin Signaling After Exercise in Insulin Receptor Substrate-2-Deficient Mice. Diabetes 2002, 51: 479-483. PMID: 11812758, DOI: 10.2337/diabetes.51.2.479.Peer-Reviewed Original ResearchConceptsPhosphotyrosine-associated phosphatidylinositolIRS-2 tyrosine phosphorylationIRS-2 signalingInsulin receptor substrate-2-deficient (IRS2(-/-)) miceWild-type miceIRS-2-deficient miceEnhanced insulin actionWT miceTyrosine phosphorylationTreadmill exerciseInsulin receptor substrateInsulin actionMiceImmediate periodSkeletal muscleInsulin-stimulated responsesInsulin signalingMarked increaseReceptor substrateExerciseInsulinPresent studySignalingPhosphorylation
1999
Irs-2 coordinates Igf-1 receptor-mediated β-cell development and peripheral insulin signalling
Withers D, Burks D, Towery H, Altamuro S, Flint C, White M. Irs-2 coordinates Igf-1 receptor-mediated β-cell development and peripheral insulin signalling. Nature Genetics 1999, 23: 32-40. PMID: 10471495, DOI: 10.1038/12631.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsApoptosisBlood GlucoseBody WeightFemaleGene Expression Regulation, DevelopmentalGlucose Tolerance TestInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, KnockoutMuscle, SkeletalPancreasPhosphoproteinsReceptor, IGF Type 1Signal TransductionTime FactorsConceptsIGF-1 receptorΒ-cell developmentIGF-1Glucose homeostasisΒ-cellsPeripheral insulin resistancePeripheral target tissuesEffect of insulinPancreatic β-cellsPeripheral insulinInsulin resistanceInsulin receptor substratePost-natal growthGlucose metabolismNull allelesTarget tissuesInsulinMiceReceptor substrateIR-1Carbohydrate metabolismReceptorsSurvivalCell growthPleiotropic effectsCharacterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats
Jiang Z, Lin Y, Clemont A, Feener E, Hein K, Igarashi M, Yamauchi T, White M, King G. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. Journal Of Clinical Investigation 1999, 104: 447-457. PMID: 10449437, PMCID: PMC408521, DOI: 10.1172/jci5971.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCalcium-Calmodulin-Dependent Protein KinasesIn Vitro TechniquesInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLiverMaleMicrocirculationObesityPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationRatsRats, ZuckerReceptor, InsulinRecombinant ProteinsSignal TransductionTyrosineConceptsObese ratsLean ratsObese ZuckerIRS-2-associated PIIndependent risk factorProtein levelsEuglycemic clamp studiesInsulin-resistant statesObese Zucker ratsSelective resistanceTyrosine phosphorylationVascular tissueInsulin resistanceInsulin infusionRisk factorsCardiovascular diseaseClamp studiesZucker ratsReceptor beta subunitAortaRatsInsulinInsulin receptor beta subunitERK 1/2Vivo studiesInsulin Receptor Substrate-2 Is Not Necessary for Insulin- and Exercise-stimulated Glucose Transport in Skeletal Muscle*
Higaki Y, Wojtaszewski J, Hirshman M, Withers D, Towery H, White M, Goodyear L. Insulin Receptor Substrate-2 Is Not Necessary for Insulin- and Exercise-stimulated Glucose Transport in Skeletal Muscle*. Journal Of Biological Chemistry 1999, 274: 20791-20795. PMID: 10409618, DOI: 10.1074/jbc.274.30.20791.Peer-Reviewed Original ResearchConceptsExercise-stimulated glucose transportInsulin-stimulated 2DG uptakeBlood glucose concentrationGlucose transportInsulin resistanceSkeletal muscleInsulin receptor substrate 2Glucose concentrationSkeletal muscle glucose transportHigher blood glucose concentrationsInsulin receptor substrate-2-deficient (IRS2(-/-)) miceOnset of diabetesType 2 diabetesWild-type miceMuscle glucose transportIRS2 proteinAbsence of insulinMuscle GLUT4 contentSubstrate 2WT animalsSoleus muscleGLUT4 contentLower basalMiceInsulin
1996
Cross-talk between the insulin and angiotensin signaling systems.
Velloso L, Folli F, Sun X, White M, Saad M, Kahn C. Cross-talk between the insulin and angiotensin signaling systems. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 12490-12495. PMID: 8901609, PMCID: PMC38019, DOI: 10.1073/pnas.93.22.12490.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsElectrophoresis, Polyacrylamide GelInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsJanus Kinase 1Janus Kinase 2Janus Kinase 3MalePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein-Tyrosine KinasesProto-Oncogene ProteinsRatsRats, WistarSignal TransductionTyrosineConceptsAngiotensin IIInjection of ANGIIEffect of AIIIRS-1/IRSAT1 receptor antagonistInsulin receptorRenal functionAT1 receptorInsulin resistanceReceptor antagonistCardiovascular diseaseAII stimulationAcute inhibitionIRS phosphorylationTyrosine phosphorylationReceptorsIRS-2Insulin-stimulated PIIRS-1G proteinsJAK2 tyrosine kinaseImportant regulatorInsulinRapid tyrosine phosphorylationTyrosine kinase