Featured Publications
Elevated circulating follistatin associates with an increased risk of type 2 diabetes
Wu C, Borné Y, Gao R, López Rodriguez M, Roell W, Wilson J, Regmi A, Luan C, Aly D, Peter A, Machann J, Staiger H, Fritsche A, Birkenfeld A, Tao R, Wagner R, Canouil M, Hong M, Schwenk J, Ahlqvist E, Kaikkonen M, Nilsson P, Shore A, Khan F, Natali A, Melander O, Orho-Melander M, Nilsson J, Häring H, Renström E, Wollheim C, Engström G, Weng J, Pearson E, Franks P, White M, Duffin K, Vaag A, Laakso M, Stefan N, Groop L, De Marinis Y. Elevated circulating follistatin associates with an increased risk of type 2 diabetes. Nature Communications 2021, 12: 6486. PMID: 34759311, PMCID: PMC8580990, DOI: 10.1038/s41467-021-26536-w.Peer-Reviewed Original ResearchConceptsAdipose tissue insulin resistanceTissue insulin resistanceType 2 diabetesFollistatin levelsGlucokinase regulatory protein geneFollistatin secretionHazard ratioInsulin resistanceNon-alcoholic fatty liver diseaseAdjusted hazard ratioFatty liver diseaseRisk of T2DFree fatty acid releaseFatty acid releaseIncident T2DLiver diseaseGenome-wide association studiesHuman adipocytesT2DAcid releaseStandard deviation increaseDiabetesSecretionRiskRegulatory protein gene
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 advancesRoleSequenceYearsErratum. Inhibition of TNF-α Improves the Bladder Dysfunction That Is Associated With Type 2 Diabetes. Diabetes 2012;61:2134–2145
Wang Z, Cheng Z, Cristofaro V, Li J, Xiao X, Gomez P, Ge R, Gong E, Strle K, Sullivan M, Adam R, White M, Olumi A. Erratum. Inhibition of TNF-α Improves the Bladder Dysfunction That Is Associated With Type 2 Diabetes. Diabetes 2012;61:2134–2145. Diabetes 2021, 70: 1416-1416. PMID: 33980694, PMCID: PMC8275895, DOI: 10.2337/db21-er06c.Peer-Reviewed Original Research
2020
From population to neuron: exploring common mediators for metabolic problems and mental illnesses
Takayanagi Y, Ishizuka K, Laursen T, Yukitake H, Yang K, Cascella N, Ueda S, Sumitomo A, Narita Z, Horiuchi Y, Niwa M, Taguchi A, White M, Eaton W, Mortensen P, Sakurai T, Sawa A. From population to neuron: exploring common mediators for metabolic problems and mental illnesses. Molecular Psychiatry 2020, 26: 3931-3942. PMID: 33173197, PMCID: PMC8514126, DOI: 10.1038/s41380-020-00939-5.Peer-Reviewed Original ResearchConceptsMajor mental illnessOlfactory neuronal cellsInsulin resistanceMental illnessBipolar disorderNeuronal cellsPathophysiological mediatorsHigh incidenceSZ patientsCommon mediatorIrs2 knockout miceSame large cohortIRS2 tyrosine phosphorylationDanish registriesBP patientsHealthy controlsHealthy subjectsLarge cohortEpidemiological dataEpidemiological studiesKnockout miceAnimal modelsPatientsMetabolic problemsDiabetes
2013
Chronic 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
2012
500 COMBINATION OF METFORMIN AND INHIBITION OF TNF-A REVERSE THE BLADDER DYSFUNCTION ASSOCIATED WITH TYPE 2 DIABETES
Wang Z, Cheng Z, Cristofaro V, Gomez P, Sullivan M, Adam R, White M, Olumi A. 500 COMBINATION OF METFORMIN AND INHIBITION OF TNF-A REVERSE THE BLADDER DYSFUNCTION ASSOCIATED WITH TYPE 2 DIABETES. Journal Of Urology 2012, 187: e205. DOI: 10.1016/j.juro.2012.02.570.Peer-Reviewed Original Research
2011
1375 BLADDER DYSFUNCTION ASSOCIATED WITH TYPE 2 DIABETES IS IMPROVED BY INHIBITION OF INFLAMMATORY AND APOPTOTIC MEDIATORS
Wang Z, Cheng Z, Cristofaro V, Li J, Gong E, Strle K, Sullivan M, Adam R, White M, Olumi A. 1375 BLADDER DYSFUNCTION ASSOCIATED WITH TYPE 2 DIABETES IS IMPROVED BY INHIBITION OF INFLAMMATORY AND APOPTOTIC MEDIATORS. Journal Of Urology 2011, 185: e549. DOI: 10.1016/j.juro.2011.02.1199.Peer-Reviewed Original Research
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
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 ResearchGenetic Deficiency of Glycogen Synthase Kinase-3β Corrects Diabetes in Mouse Models of Insulin Resistance
Tanabe K, Liu Z, Patel S, Doble B, Li L, Cras-Méneur C, Martinez S, Welling C, White M, Bernal-Mizrachi E, Woodgett J, Permutt M. Genetic Deficiency of Glycogen Synthase Kinase-3β Corrects Diabetes in Mouse Models of Insulin Resistance. PLOS Biology 2008, 6: e37. PMID: 18288891, PMCID: PMC2245985, DOI: 10.1371/journal.pbio.0060037.Peer-Reviewed Original ResearchConceptsBeta-cell massIrs2-/- miceInsulin resistanceMouse modelType 2 diabetes mellitusObese insulin-resistant individualsWhole-body glucose disposalOnset of diabetesPdx1 levelsBeta-cell functionBeta-cell lossInsulin-resistant individualsBeta-cell replicationGSK-3betaBeta-cell proliferationInsulin receptor substrate 2Cyclin-dependent kinase inhibitorDiabetes mellitusDiabetes onsetEarly diabetesPI-3K/Akt pathwayGlucose disposalGSK-3beta activityDiabetesInsulin action
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
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 ResearchConceptsRIP-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 systemSecretionCyclins 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
Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes
Lin X, Taguchi A, Park S, Kushner J, Li F, Li Y, White M. Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes. Journal Of Clinical Investigation 2004, 114: 908-916. PMID: 15467829, PMCID: PMC518668, DOI: 10.1172/jci22217.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody WeightBrainDiabetes Mellitus, Type 2DietEatingGene DeletionGene Expression RegulationGlucoseHomeostasisHumansHypothalamusInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansMaleMiceMice, Inbred C57BLMice, KnockoutObesityPhosphoproteinsRandom AllocationSignal TransductionConceptsInsulin receptor substrate 2Beta cellsInsulin resistanceSufficient beta cell functionPancreas beta cellsBeta-cell failureBeta-cell functionFunctional beta cellsMonths of ageAdult beta cellsFat body massSubstrate 2Obese miceDiabetesΒ-cellsObesityPromotes RegenerationConditional knockoutCell functionMiceBrainBody massMolecular linkCell failureCellsIslet-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 TransductionSomatomedinsUpregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes
Hennige A, Burks D, Ozcan U, Kulkarni R, Ye J, Park S, Schubert M, Fisher T, Dow M, Leshan R, Zakaria M, Mossa-Basha M, White M. Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes. Journal Of Clinical Investigation 2003, 112: 1521-1532. PMID: 14617753, PMCID: PMC259126, DOI: 10.1172/jci18581.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell SizeDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Dietary FatsGene Expression RegulationHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansIslets of Langerhans TransplantationMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPhosphoproteinsReceptor, InsulinSignal TransductionSurvival RateUp-RegulationConceptsPancreatic beta-cell functionPeripheral insulin actionBeta-cell failureBeta-cell functionType 2 diabetesIrs2-/- miceInsulin receptor substrate 2Beta-cell growthBeta cell-specific expressionPrevents diabetesObese miceTransgenic isletsInsulin secretionWT isletsIRS2 expressionPharmacological approachesBeta cellsPhysiologic responsesInsulin actionRational treatmentDiabetesInsulin/IGFCell functionMiceCell-specific expressionInsulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation
Schubert M, Brazil D, Burks D, Kushner J, Ye J, Flint C, Farhang-Fallah J, Dikkes P, Warot X, Rio C, Corfas G, White M. Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation. Journal Of Neuroscience 2003, 23: 7084-7092. PMID: 12904469, PMCID: PMC6740672, DOI: 10.1523/jneurosci.23-18-07084.2003.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsApoptosisBody WeightBrainCell CountCell DivisionCell SurvivalCells, CulturedCerebellumCrosses, GeneticEnzyme InhibitorsHeterozygoteIn Situ Nick-End LabelingInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutNeuronsOrgan SizePhosphoproteinsPhosphorylationReceptor, IGF Type 1Signal TransductionTau ProteinsConceptsMolecular linkInsulin receptor substrate (IRS) proteinsBrain growthNeurodegenerative diseasesPancreatic beta-cell functionPeripheral insulin actionSubstrate proteinsBeta-cell functionTyrosine phosphorylationLike growth factorIrs2 branchInsulin resistanceTau phosphorylationIRS2 geneNeuronal proliferationInsulin actionMouse brainInsulin-IGFGrowth factorPhosphorylationIRS2DiabetesBody growthDiseaseMice
2002
Pdx1 restores β cell function in Irs2 knockout mice
Kushner J, Ye J, Schubert M, Burks D, Dow M, Flint C, Dutta S, Wright C, Montminy M, White M. Pdx1 restores β cell function in Irs2 knockout mice. Journal Of Clinical Investigation 2002, 109: 1193-1201. PMID: 11994408, PMCID: PMC150960, DOI: 10.1172/jci14439.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBlood GlucoseBody WeightDiabetes Mellitus, Type 2FemaleHomeodomain ProteinsInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansMaleMiceMice, KnockoutPhosphoproteinsReceptor, InsulinSignal TransductionTrans-ActivatorsConceptsOnset of diabetesPeripheral insulin actionBeta-cell failureType 2 diabetesBeta-cell massEarly-onset diabetesIrs2 knockout micePancreatic beta-cell growthBeta-cell growthWeeks of ageIrs2 branchHepatocyte nuclear factorGlucose toleranceExpression of Pdx1Knockout miceBeta cellsDiabetesInsulin actionInsulin/MiceNuclear factorTranscription factor Pdx1Cell functionIsletsTransgenic expression