2012
Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2
Copps K, White M. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia 2012, 55: 2565-2582. PMID: 22869320, PMCID: PMC4011499, DOI: 10.1007/s00125-012-2644-8.Peer-Reviewed Original ResearchConceptsInsulin receptor substrateT phosphorylationReceptor substrateSerine/threonine residuesSerine/threonine phosphorylationInsulin receptor tyrosine kinaseInsulin-stimulated kinasesReceptor tyrosine kinasesThreonine phosphorylationThreonine residuesNegative regulationTyrosine kinasePhosphorylationCultured cellsKinaseMetabolic diseasesIRS2IRS1Hormonal controlKey targetAltered patternTail regionComplex mechanismsRegulationDysregulation
2007
Analysis of compensatory β-cell response in mice with combined mutations of Insr and Irs2
Kim J, Kido Y, Scherer P, White M, Accili D. Analysis of compensatory β-cell response in mice with combined mutations of Insr and Irs2. AJP Endocrinology And Metabolism 2007, 292: e1694-e1701. PMID: 17299086, DOI: 10.1152/ajpendo.00430.2006.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAdiponectinAdipose TissueAnimalsAnimals, NewbornDiabetes MellitusGlucose Tolerance TestGrowth DisordersHyperinsulinismInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsLeptinLiverMiceMice, Inbred StrainsMice, KnockoutMuscle, SkeletalMutationOrgan SizeOsmolar ConcentrationPhosphatidylinositol 3-KinasesPhosphoproteinsProto-Oncogene Proteins c-aktReceptor, InsulinConceptsBeta-cell dysfunctionBeta-cell massInsulin resistanceInsulin secretionType 2 diabetes resultsCompensatory insulin secretionBeta-cell responseImpaired insulin actionType 2 diabetesΒ-cell responseBeta-cell growthBeta-cell physiologyDiabetes resultsInsulin levelsMetabolic controlInsulin actionProgressive deteriorationDiabetesRobust increaseDysfunctionCompensatory responseMiceSecretionComprehensive treatmentINSR
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
2005
Cyclins D2 and D1 Are Essential for Postnatal Pancreatic β-Cell Growth
Kushner J, Ciemerych M, Sicinska E, Wartschow L, Teta M, Long S, Sicinski P, White M. Cyclins D2 and D1 Are Essential for Postnatal Pancreatic β-Cell Growth. Molecular And Cellular Biology 2005, 25: 3752-3762. PMID: 15831479, PMCID: PMC1084308, DOI: 10.1128/mcb.25.9.3752-3762.2005.Peer-Reviewed Original ResearchConceptsBeta-cell massAdult beta-cell massD2 mRNA expressionCyclin D2 mRNA expressionBeta-cell proliferationMonths of agePancreatic β-cell growthBeta cell expansionΒ-cell growthGlucose intoleranceGlucose toleranceInsulin secretionGlucose homeostasisAdult miceBeta cellsIslet growthPancreatic isletsCyclin D1MRNA expressionDiabetesMiceCyclin D2Cyclin D3Adult murineIslet development
2004
Insulin receptor substrate proteins and diabetes
Lee Y, White M. Insulin receptor substrate proteins and diabetes. Archives Of Pharmacal Research 2004, 27: 361-370. PMID: 15180298, DOI: 10.1007/bf02980074.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate (IRS) proteinsSubstrate proteinsPancreatic β-cell growthInsulin/IGFIntracellular signaling cascadesReceptor tyrosine kinasesΒ-cell growthCell surface receptorsIRS proteinsGrowth factor actionProtein signalingSerine phosphorylationSignaling cascadesInsulin resistanceTyrosine kinaseInsulin-like growth factor actionIrs2 branchCell growthSurface receptorsFactor actionPeripheral insulin responsePeripheral insulin resistanceIRS2ProteinImportant mechanism
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 TransductionSomatomedinscAMP promotes pancreatic β-cell survival via CREB-mediated induction of IRS2
Jhala U, Canettieri G, Screaton R, Kulkarni R, Krajewski S, Reed J, Walker J, Lin X, White M, Montminy M. cAMP promotes pancreatic β-cell survival via CREB-mediated induction of IRS2. Genes & Development 2003, 17: 1575-1580. PMID: 12842910, PMCID: PMC196130, DOI: 10.1101/gad.1097103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell LineCell SurvivalColforsinCyclic AMPCyclic AMP Response Element-Binding ProteinDiabetes MellitusGene Expression RegulationGlucagonGlucagon-Like Peptide 1GlucoseGlucose IntoleranceHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansMiceMice, TransgenicPeptide FragmentsPhosphoproteinsPhosphorylationPromoter Regions, GeneticProtein PrecursorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionTransfectionTransgenesTumor Cells, CulturedConceptsPancreatic β-cell survivalActivity of CREBSecond messenger cAMPSurvival kinase AktΒ-cell survivalKinase AktPathway componentsA-CREBCREB actionExpression of IRS2Cell survivalBeta-cell apoptosisDirect targetIslet cell survivalNovel mechanismCREBIRS2ExpressionCAMPInductionTransgeneAktIGF-1ApoptosisSurvival
2002
IRS proteins and the common path to diabetes
White M. IRS proteins and the common path to diabetes. AJP Endocrinology And Metabolism 2002, 283: e413-e422. PMID: 12169433, DOI: 10.1152/ajpendo.00514.2001.Peer-Reviewed Original ResearchConceptsInsulin receptor substrate (IRS) proteinsIRS protein functionsProteosome-mediated degradationCommon regulatory pathwayCommon molecular mechanismIntracellular signaling cascadesInsulin/IGF receptorIRS-2 signalingCell surface receptorsIRS proteinsSubstrate proteinsPancreatic beta-cell growthProtein functionGrowth factor actionNutrient sensingSerine phosphorylationRegulatory pathwaysSignaling cascadesIGF-signaling pathwayInsulin resistanceMolecular mechanismsIRS-2Insulin-like growth factor actionIRS-1Broader role
1996
Insulin Signal Transduction and the IRS Proteins
Myers M, White M. Insulin Signal Transduction and the IRS Proteins. The Annual Review Of Pharmacology And Toxicology 1996, 36: 615-658. PMID: 8725404, DOI: 10.1146/annurev.pa.36.040196.003151.Peer-Reviewed Original ResearchConceptsIRS proteinsIntracellular tyrosine kinaseBinding of SH2Numerous intracellular signalsTyrosine phosphorylation sitesReceptor-mediated phosphorylationInsulin signal transductionPTB domainCellular physiologyPhosphorylation sitesSignal transductionIntracellular signalsExtracellular domainTyrosine kinaseCytokine receptorsBiochemical eventsInsulin receptorGlucose transportProteinPhosphorylationSignalingGrowth factorSpecific receptorsExciting moleculesPropagation of signals