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 evidenceInsulinChronic activation of a designer Gq-coupled receptor improves β cell function
Jain S, de Azua I, Lu H, White M, Guettier J, Wess J. Chronic activation of a designer Gq-coupled receptor improves β cell function. Journal Of Clinical Investigation 2013, 123: 1750-1762. PMID: 23478411, PMCID: PMC3613926, DOI: 10.1172/jci66432.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationClozapineDiabetes Mellitus, ExperimentalDrug Evaluation, PreclinicalFemaleGene ExpressionGTP-Binding Protein alpha Subunits, Gq-G11Hypoglycemic AgentsInsulin Receptor Substrate ProteinsInsulin-Secreting CellsMaleMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, TransgenicMolecular Targeted TherapyMuscarinic AgonistsProtein EngineeringReceptor, Muscarinic M3Receptors, G-Protein-CoupledRecombinant ProteinsConceptsΒ-cell functionΒ-cellsCell functionPancreatic β-cell functionStreptozotocin-induced diabetesBeneficial metabolic effectsTreatment of T2D.High-fat dietType 2 diabetesNovel antidiabetic drugsType G proteinsClasses of receptorsChronic stimulationMetabolic deficitsAntidiabetic drugsMetabolic effectsChronic activationGlucose homeostasisTherapeutic strategiesCell pathwaysEnhanced expressionReceptorsNumerous receptorsCellular effectsDiabetes
2010
Extreme makeover of pancreatic α-cells
Zaret K, White M. Extreme makeover of pancreatic α-cells. Nature 2010, 464: 1132-1133. PMID: 20414295, PMCID: PMC3982719, DOI: 10.1038/4641132a.Peer-Reviewed Original Research
2009
Insulin Receptor Substrate-2 in β-Cells Decreases Diabetes in Nonobese Diabetic Mice
Norquay L, D'Aquino K, Opare-Addo L, Kuznetsova A, Haas M, Bluestone J, White M. Insulin Receptor Substrate-2 in β-Cells Decreases Diabetes in Nonobese Diabetic Mice. Endocrinology 2009, 150: 4531-4540. PMID: 19574401, PMCID: PMC2754683, DOI: 10.1210/en.2009-0395.Peer-Reviewed Original ResearchConceptsNonobese diabetic (NOD) miceBeta-cell destructionNOD miceInsulin receptor substrate 2Glucose toleranceDiabetes incidenceDiabetic miceIslet massAnti-CD3 antibody injectionNondiabetic NOD miceReduced diabetes incidenceRisk of diabetesBeta-cell massType 1 diabetesBetter glucose toleranceAnti-CD3 antibodyBeta-cell growthWk of ageDiabetic NODSevere insulitisOvert diabetesSubstrate 2C57BL/6 miceBeta-cell mitogenesisAntibody injection
2007
The Repression of IRS2 Gene by ATF3, a Stress-Inducible Gene, Contributes to Pancreatic β-Cell Apoptosis
Li D, Yin X, Zmuda E, Wolford C, Dong X, White M, Hai T. The Repression of IRS2 Gene by ATF3, a Stress-Inducible Gene, Contributes to Pancreatic β-Cell Apoptosis. Diabetes 2007, 57: 635-644. PMID: 18057093, DOI: 10.2337/db07-0717.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 3AnimalsApoptosisCell LineCells, CulturedDown-RegulationInsulinInsulin Receptor Substrate ProteinsInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutPhosphoproteinsPromoter Regions, GeneticRatsStress, PhysiologicalTime FactorsConceptsStress-inducible genesIRS2 gene expressionIRS2 promoterBinding of ATF3Gene transcriptionGene expressionExpression of IRS2Chromatin immunoprecipitation assaysIRS2 genePancreatic β-cell apoptosisEnvironmental stress factorsΒ-cell apoptosisTranscription factor 3Effect of ATF3Stress signalsImmunoprecipitation assaysBeta-cell survivalTarget genesProapoptotic genesExpression of ATF3GenesTranscriptionIRS2 expressionATF3PromoterAnalysis 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
RIP-Cre Revisited, Evidence for Impairments of Pancreatic β-Cell Function*
Lee J, Ristow M, Lin X, White M, Magnuson M, Hennighausen L. RIP-Cre Revisited, Evidence for Impairments of Pancreatic β-Cell Function*. Journal Of Biological Chemistry 2005, 281: 2649-2653. PMID: 16326700, DOI: 10.1074/jbc.m512373200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene TargetingGlucose IntoleranceInsulinInsulin-Secreting CellsIntegrasesMaleMiceMice, TransgenicPromoter Regions, GeneticRatsConceptsRIP-Cre miceRIP-CreGlucose intolerancePancreatic β-cell functionΒ-cell functionFrank diabetesInsulin secretionRat insulin II gene promoterTransgenic miceMiceCre recombinaseIntoleranceMolecular underpinningsConditional geneDiabetesGene promoterGenetic pathwaysCre/loxP recombinase systemGenesLoxP sitesImpairmentRecombinase systemSecretionExendin-4 Uses Irs2 Signaling to Mediate Pancreatic β Cell Growth and Function*
Park S, Dong X, Fisher T, Dunn S, Omer A, Weir G, White M. Exendin-4 Uses Irs2 Signaling to Mediate Pancreatic β Cell Growth and Function*. Journal Of Biological Chemistry 2005, 281: 1159-1168. PMID: 16272563, DOI: 10.1074/jbc.m508307200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseCell LineCell SurvivalCyclic AMPDose-Response Relationship, DrugElectrophoresis, Polyacrylamide GelExenatideGenotypeGlucagon-Like Peptide-1 ReceptorGlucoseGuinea PigsHumansHyperglycemiaImmunoblottingImmunohistochemistryImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin SecretionInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsIslets of LangerhansMiceMice, TransgenicModels, BiologicalModels, ChemicalPancreasPeptidesPhosphoproteinsPhosphorylationReceptor, InsulinReceptors, GlucagonReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSignal TransductionTime FactorsVenomsConceptsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsReceptor agonistExendin-4Beta cellsProgressive beta cell lossShort-term therapeutic effectsInsulin-like growth factorBeta-cell lossProgression of diabetesBeta-cell massBeta-cell replicationBeta-cell growthPancreatic β-cell growthΒ-cell growthIrs2 branchPrevents diabetesInsulin/insulin-like growth factorCell growthInsulin secretionTherapeutic effectIRS2 expressionLong-term effectsFatal diabetesCell lossPhosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis*
Kushner J, Simpson L, Wartschow L, Guo S, Rankin M, Parsons R, White M. Phosphatase and Tensin Homolog Regulation of Islet Growth and Glucose Homeostasis*. Journal Of Biological Chemistry 2005, 280: 39388-39393. PMID: 16170201, DOI: 10.1074/jbc.m504155200.Peer-Reviewed Original ResearchConceptsInsulin/insulin-like growth factorWild typeIrs2 branchBeta-cell growthInsulin-like growth factorPhosphatase PTENGrowth factorFoxO1 phosphorylationBeta-cell massPTEN expressionAktPTENCascadeSmall isletsGlucose homeostasisInsulin productionGrowthIslet growthSufficient insulinPhosphatidylinositolTolerancePhosphorylationMiceSignalingHomeostasis