Featured Publications
Lower Hepatic Fat Is Associated With Improved Insulin Secretion in a High-Risk Prediabetes Subphenotype During Lifestyle Intervention
Wagner R, Heni M, Kantartzis K, Sandforth A, Machann J, Schick F, Peter A, Fritsche L, Szendrödi J, Pfeiffer A, Schürmann A, Blüher M, Hauner H, Seissler J, Bornstein S, Roden M, Stefan N, Birkenfeld A, White M, Häring H, Fritsche A. Lower Hepatic Fat Is Associated With Improved Insulin Secretion in a High-Risk Prediabetes Subphenotype During Lifestyle Intervention. Diabetes 2022, 72: 362-366. PMID: 36525512, PMCID: PMC9935494, DOI: 10.2337/db22-0441.Peer-Reviewed Original ResearchConceptsInsulin secretionLifestyle interventionLiver fatOral glucose tolerance testHigh liver fatLifestyle intervention studyGlucose tolerance testHigh-risk clustersHepatic fatTolerance testInsulin sensitivitySpecific subphenotypesIntervention studiesSecretionTime pointsInterventionPrediabetesGlycemic traitsFatSubphenotypesGlycemiaCluster 3
2019
1835-P: Deletion of Insulin Receptor Substrate 2 in AGRP Neurons Causes Beta-Cell Dysfunction
TAO R, COPPS K, WHITE M, STOEHR O. 1835-P: Deletion of Insulin Receptor Substrate 2 in AGRP Neurons Causes Beta-Cell Dysfunction. Diabetes 2019, 68 DOI: 10.2337/db19-1835-p.Peer-Reviewed Original ResearchAgRP neuronsArcuate nucleusInsulin resistanceInsulin secretionInsulin receptor substrateType 2 diabetes progressesCompensatory insulin secretionL-arginine treatmentBeta-cell compensationBeta-cell dysfunctionPeripheral insulin resistanceBeta-cell failureBeta-cell functionHigh-fat dietInsulin secretory functionType 2 diabetesSteady-state hyperglycemiaGlucose infusion rateΒ-cell dysfunctionInsulin receptor substrate 2Pancreatic β-cellsGrowth-promoting actionDiabetes progressesFat dietHyperglycemic clamp
2012
Pulsatile Portal Vein Insulin Delivery Enhances Hepatic Insulin Action and Signaling
Matveyenko A, Liuwantara D, Gurlo T, Kirakossian D, Man C, Cobelli C, White M, Copps K, Volpi E, Fujita S, Butler P. Pulsatile Portal Vein Insulin Delivery Enhances Hepatic Insulin Action and Signaling. Diabetes 2012, 61: 2269-2279. PMID: 22688333, PMCID: PMC3425431, DOI: 10.2337/db11-1462.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2DogsForkhead Transcription FactorsGlucokinaseInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceInsulin SecretionLiverMaleNerve Tissue ProteinsPortal VeinProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleySignal TransductionConceptsPulsatile insulin secretionHepatic insulin actionInsulin secretionHepatic insulinPortal veinInsulin deliveryPulsatile patternInsulin actionDiscrete insulin secretory burstsHepatic insulin receptor substrateImpaired activationType 2 diabetes mellitusSequential liver biopsiesIntraportal insulin infusionInsulin secretory burstsHepatic insulin resistanceHepatic portal veinExpression of glucokinaseGlycemic controlDiabetes mellitusLiver biopsyInsulin resistanceInsulin infusionSecretory burstsRat model
2010
Chapter 331 IRS-Protein Scaffolds and Insulin/IGF Action in Central and Peripheral Tissues
White M. Chapter 331 IRS-Protein Scaffolds and Insulin/IGF Action in Central and Peripheral Tissues. 2010, 2873-2883. DOI: 10.1016/b978-0-12-374145-5.00331-4.Peer-Reviewed Original ResearchInsulin-like growth factor signalsInsulin-like receptorGrowth factor signalsΒ-cell growthIRS proteinsNutrient homeostasisFactor signalsAdapter moleculeSystemic growthInsulin receptorSimilar signalingInsulin targetsRational platformCommon systemic disordersType 2 diabetesCascadePhysiologic roleInsulin actionInsulin resistanceSystemic disordersIGF actionInsulin responseInsulin secretionCardiovascular diseaseDiabetic tissues
2009
The Role of Insulin‐like Signaling for the Central and Peripheral Regulation of Nutrient Homeostasis and Life Span
White M. The Role of Insulin‐like Signaling for the Central and Peripheral Regulation of Nutrient Homeostasis and Life Span. The FASEB Journal 2009, 23: 329.2-329.2. DOI: 10.1096/fasebj.23.1_supplement.329.2.Peer-Reviewed Original ResearchInsulin-like signalingNutrient homeostasisHigher animalsInsulin receptor substrateLife spanAge-related diseasesMammalian lifespanLower metazoansReceptor substrateInsulin resistanceInsulin secretionNutrient storageNarrow physiologic rangeSignalingMetazoansAction of insulinReduced insulin secretionRole of insulinHomeostasisBlood glucose concentrationCompensatory hyperinsulinemiaGlucose intolerancePeripheral regulationPeripheral tissuesGlucose homeostasis
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 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 lossCyclins 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
2003
Upregulation 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 expressionChapter 72 IRS-Protein Scaffolds and Insulin/IGF Action
White M. Chapter 72 IRS-Protein Scaffolds and Insulin/IGF Action. 2003, 409-419. DOI: 10.1016/b978-012124546-7/50433-2.Peer-Reviewed Original ResearchIRS protein familyMultiple biological processesIRS proteinsIL-9 signalingTissue agingBiological processesIRS-2Growth controlPeripheral insulin sensitivityPeripheral insulin actionType 2 diabetesPancreatic p-cellsCell functionIRS2IGF actionIL-4Insulin sensitivityInflammatory responseInsulin actionInsulin secretionIL-7Immune responseFundamental roleTumor growthP cells
2002
Defective insulin secretion in pancreatic β cells lacking type 1 IGF receptor
Xuan S, Kitamura T, Nakae J, Politi K, Kido Y, Fisher P, Morroni M, Cinti S, White M, Herrera P, Accili D, Efstratiadis A. Defective insulin secretion in pancreatic β cells lacking type 1 IGF receptor. Journal Of Clinical Investigation 2002, 110: 1011-1019. PMID: 12370279, PMCID: PMC151144, DOI: 10.1172/jci15276.Peer-Reviewed Original ResearchConceptsType 1 IGF receptorBeta-cell massDefective insulin secretionInsulin secretionIGF receptorInsulin releaseInadequate compensatory increaseGlucose-dependent insulin releaseBeta-cell proliferationAge-dependent impairmentPancreatic β-cellsGlucose toleranceDecrease of glucoseBeta cellsType 2Compensatory increaseCell massΒ-cellsReceptor tyrosine kinasesSecretionCell proliferationAntiapoptotic roleReceptorsTyrosine kinaseConditional mutagenesis
2000
Dysregulation of IRS-proteins causes insulin resistance and diabetes
Aguirre V, White M. Dysregulation of IRS-proteins causes insulin resistance and diabetes. Current Opinion In Endocrinology Diabetes And Obesity 2000, 7: 1-7. DOI: 10.1097/00060793-200002000-00001.Peer-Reviewed Original ResearchIRS proteinsInsulin receptor substrate (IRS) proteinsInsulin/insulin-like growth factorPeripheral insulin resistanceType 2 diabetesInsulin resistanceSubstrate proteinsGenetic approachesCommon type 2 diabetesΒ-cell failureInsulin-like growth factorCompensatory insulin secretionDevelopment of diabetesNormal carbohydrate metabolismEarly-onset formCarbohydrate metabolismGrowth factorInsulin secretionDiabetesInsulin actionImportant insightsDysregulationSecretionProteinResistanceDysregulation of IRS-proteins causes insulin resistance and diabetes
Aguirre V, White M. Dysregulation of IRS-proteins causes insulin resistance and diabetes. Current Opinion In Endocrinology Diabetes And Obesity 2000, 7: 1. DOI: 10.1097/00075197-200002000-00001.Peer-Reviewed Original ResearchIRS proteinsPeripheral insulin resistanceInsulin receptor substrate (IRS) proteinsInsulin/insulin-like growth factorType 2 diabetesΒ-cell differentiationInsulin-like growth factorInsulin receptor substrateCompensatory insulin secretionChronic insulin resistanceInsulin resistanceInsulin-signaling pathwayCarbohydrate metabolismInsulin secretionSubstrate proteinsGrowth factorSignal transductionTranscription factorsGenetic approachesCommon type 2 diabetesMolecular basisPancreatic β-cellsReceptor substrateInsulin actionInsulin-signaling system
1999
Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of their relation with alterations in insulin secretion and insulin sensitivity
Almind K, Frederiksen S, Bernal D, Hansen T, Ambye L, Urhammer S, Ekstrøm C, Berglund L, Reneland R, Lithell H, White M, Van Obberghen E, Pedersen O. Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of their relation with alterations in insulin secretion and insulin sensitivity. Diabetologia 1999, 42: 1244-1249. PMID: 10525667, DOI: 10.1007/s001250051299.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAmino Acid SubstitutionBase SequenceDiabetes Mellitus, Type 2Gene FrequencyGenetic Carrier ScreeningGenetic TestingGlucose Tolerance TestHumansInsulinInsulin Receptor Substrate ProteinsInsulin SecretionIntracellular Signaling Peptides and ProteinsMaleMiddle AgedMolecular Sequence DataPedigreePhosphoproteinsPhosphotyrosinePolymorphism, Single-Stranded ConformationalPromoter Regions, GeneticProspective StudiesTwo-Hybrid System TechniquesConceptsType II diabetic patientsII diabetic patientsSerum insulin concentrationsInsulin secretionDiabetic patientsInsulin sensitivityInsulin concentrationsGly1057Asp variantInsulin receptor substrate-2 (IRS-2) geneIntravenous glucose tolerance testGlucose-tolerant offspringGlucose tolerance testGlucose-tolerant subjectsIRS-2Elderly Swedish menMiddle-aged subjectsYoung healthy subjectsAmino acid variantsWildtype carriersDiabetic parentsTolerance testTolerant subjectsHealthy subjectsStudy groupInsulin sensivity
1998
Disruption of IRS-2 causes type 2 diabetes in mice
Withers D, Gutierrez J, Towery H, Burks D, Ren J, Previs S, Zhang Y, Bernal D, Pons S, Shulman G, Bonner-Weir S, White M. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 1998, 391: 900-904. PMID: 9495343, DOI: 10.1038/36116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseCloning, MolecularDiabetes Mellitus, Type 2FemaleGene TargetingHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, Inbred C57BLMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationReceptor, InsulinRecombination, GeneticSignal TransductionConceptsType 2 diabetesInsulin resistanceHuman type 2 diabetesPancreatic β-cell functionInsulin secretion increasesSingle molecular abnormalityΒ-cell compensationIRS-2-deficient miceΒ-cell functionHuman type 2Insulin secretionInsulin receptor substrateGlucose homeostasisSecretion increasesInsulin actionType 2DiabetesMolecular abnormalitiesProgressive deteriorationSkeletal muscleIRS-2Insulin signalingIRS-1Mild resistanceMice