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
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
2016
IRS proteins and diabetic complications
Lavin D, White M, Brazil D. IRS proteins and diabetic complications. Diabetologia 2016, 59: 2280-2291. PMID: 27514532, PMCID: PMC5506098, DOI: 10.1007/s00125-016-4072-7.Peer-Reviewed Original ResearchConceptsIRS proteinsType 2 diabetesDiabetic complicationsMitogen-activated protein kinaseElicit cellular responsesCoronary artery diseaseElevated blood glucoseComplications of diabetesProtein kinaseDownstream effectorsAdaptor moleculeInsulin signalingCellular responsesNumber of organsInsulin receptorMacrovascular complicationsMicrovascular complicationsArtery diseasePatient morbidityBlood glucoseProteinMale micePatient outcomesCell proliferationComplications
2014
IRS2 integrates insulin/IGF1 signalling with metabolism, neurodegeneration and longevity
White M. IRS2 integrates insulin/IGF1 signalling with metabolism, neurodegeneration and longevity. Diabetes Obesity And Metabolism 2014, 16: 4-15. PMID: 25200290, DOI: 10.1111/dom.12347.Peer-Reviewed Original ResearchConceptsInsulin/IGF1Central nervous systemInsulin-like signalingLife spanOrganisms showsCellular functionsNutrient homeostasisInsulin resistanceGenetic manipulationSystemic insulin resistanceClinical Alzheimer's diseaseType 2 diabetesEnergy homeostasisNeurodegenerative diseasesMetabolismNeurodegenerationCompensatory hyperinsulinaemiaHomeostasisProgressive neurodegenerationSystemic metabolismIGF1Excess insulinNervous systemAlzheimer's diseaseClinical perspectiveMP17-14 CORRECTION OF HYPERGLYCEMIA AND HYPERINSULINEMIA BY GENETIC MODIFICATION RESTORES BLADDER DYSFUNCTION ASSOCIATED WITH TYPE 2 DIABETES
Wang Z, Cristofaro V, Cheng Z, Cao H, Kreydin E, Gabrielsen J, Ge R, Wu S, Cai C, Wu P, Sullivan M, White M, Olumi A. MP17-14 CORRECTION OF HYPERGLYCEMIA AND HYPERINSULINEMIA BY GENETIC MODIFICATION RESTORES BLADDER DYSFUNCTION ASSOCIATED WITH TYPE 2 DIABETES. Journal Of Urology 2014, 191: e140-e141. DOI: 10.1016/j.juro.2014.02.547.Peer-Reviewed Original ResearchType 2 diabetesBladder dysfunction
2013
Myocardial Loss of IRS1 and IRS2 Causes Heart Failure and Is Controlled by p38α MAPK During Insulin Resistance
Qi Y, Xu Z, Zhu Q, Thomas C, Kumar R, Feng H, Dostal D, White M, Baker K, Guo S. Myocardial Loss of IRS1 and IRS2 Causes Heart Failure and Is Controlled by p38α MAPK During Insulin Resistance. Diabetes 2013, 62: 3887-3900. PMID: 24159000, PMCID: PMC3806607, DOI: 10.2337/db13-0095.Peer-Reviewed Original ResearchConceptsIRS2 proteinGene expressionType 2 diabetesEnergy metabolism gene expressionInsulin resistanceMetabolic gene expressionBox class ODouble knockout miceHeart failureActivation of p38Chronic insulin exposureActivation of p38αMetabolism gene expressionProtein kinaseRole of IRS1Cellular metabolismMolecular mechanismsInsulin receptorNeonatal rat ventricular cardiomyocytesP38α MAPKCause heart failureCellular dysfunctionIRS1Myocardial insulin resistanceClass OChronic 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
Evaluation of the Association between Maternal Smoking, Childhood Obesity, and Metabolic Disorders: A National Toxicology Program Workshop Review
Behl M, Rao D, Aagaard K, Davidson T, Levin E, Slotkin T, Srinivasan S, Wallinga D, White M, Walker V, Thayer K, Holloway A. Evaluation of the Association between Maternal Smoking, Childhood Obesity, and Metabolic Disorders: A National Toxicology Program Workshop Review. Environmental Health Perspectives 2012, 121: 170-180. PMID: 23232494, PMCID: PMC3569686, DOI: 10.1289/ehp.1205404.Peer-Reviewed Original ResearchConceptsMaternal smokingChildhood obesityMetabolic disordersRisk factorsChildhood overweight/obesityUnmeasured residual confoundingOverweight/obesityRisk of obesityCurrent epidemiological dataType 2 diabetesPotential risk factorsType 1 diabetesEarly life exposureEnvironmental chemicalsExperimental animal studiesPerinatal exposureMetabolic syndromeNicotine exposureMetabolic outcomesResidual confoundingEpidemiological dataCigarette smokeObesitySmokingAnimal studiesInhibition of TNF-α Improves the Bladder Dysfunction That Is Associated With Type 2 Diabetes
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. Inhibition of TNF-α Improves the Bladder Dysfunction That Is Associated With Type 2 Diabetes. Diabetes 2012, 61: 2134-2145. PMID: 22688336, PMCID: PMC3402324, DOI: 10.2337/db11-1763.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 2Disease Models, AnimalInsulin Receptor Substrate ProteinsMetforminMiceMice, KnockoutMuscle ContractionMyosin Light ChainsReceptors, Tumor Necrosis Factor, Type IRho-Associated KinasesTumor Necrosis Factor-alphaUp-RegulationUrinary BladderUrinary Bladder DiseasesUrinary Bladder, OveractiveConceptsDiabetic bladder dysfunctionTumor necrosis factorType 2 diabetesBladder dysfunctionDKO animalsPrimary cultured bladder smooth muscle cellsSoluble TNF receptor 1Bladder smooth muscle tissueInhibition of TNFCultured bladder smooth muscle cellsAppropriate animal modelsBladder smooth muscle cellsTNF receptor 1Smooth muscle cellsRho-kinase activitySmooth muscle tissueInsulin receptor substrate-1Detrusor hypoactivityUrologic complicationsDetrusor overactivitySystemic treatmentDiabetic patientsClinical featuresBladder fillingVoided volume500 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
Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3β?
Carew R, Sadagurski M, Goldschmeding R, Martin F, White M, Brazil D. Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3β? BMC Developmental Biology 2010, 10: 73. PMID: 20604929, PMCID: PMC2910663, DOI: 10.1186/1471-213x-10-73.Peer-Reviewed Original ResearchConceptsIrs2-/- miceYes-associated proteinKidney sizeΒ-cateninΒ-catenin targetsBody weight ratioImportant novel mediatorType 2 diabetesPostnatal day 5Mouse developmentInhibition of GSK3βOrgan sizeYAP activityYAP phosphorylationPituitary developmentDevelopmental defectsYAP levelsGlomerular densityRenal growthNeuronal proliferationAnalysis of insulinGlomerular numberConcomitant accumulationDay 5Kidney structureChapter 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
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
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
Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents
Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. Journal Of Clinical Investigation 2005, 115: 3587-3593. PMID: 16284649, PMCID: PMC1280967, DOI: 10.1172/jci25151.Peer-Reviewed Original ResearchMeSH KeywordsBiopsyBlood GlucoseBlotting, WesternBody Mass IndexBody WeightDiabetes Mellitus, Type 2DNA, MitochondrialFamily HealthFemaleGene Expression RegulationGlucose Clamp TechniqueGlucose Tolerance TestHumansHyperinsulinismImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLipidsMaleMicroscopy, ElectronMicroscopy, Electron, TransmissionMitochondriaMusclesPhosphoproteinsPhosphorylationProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSerineSignal TransductionTime FactorsTranscription, GeneticTriglyceridesConceptsInsulin-resistant offspringIR offspringType 2 diabetesInsulin-stimulated muscle glucose uptakeType 2 diabetic parentsIntramyocellular lipid contentHyperinsulinemic-euglycemic clampMuscle glucose uptakeIRS-1 serine phosphorylationMuscle mitochondrial densityMitochondrial densityMuscle biopsy samplesSerine kinase cascadeInsulin-stimulated Akt activationDiabetic parentsInsulin resistanceControl subjectsBiopsy samplesGlucose uptakeLipid accumulationMitochondrial dysfunctionInsulin signalingAkt activationEarly defectsMuscleDeletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice
Uchida T, Nakamura T, Hashimoto N, Matsuda T, Kotani K, Sakaue H, Kido Y, Hayashi Y, Nakayama K, White M, Kasuga M. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nature Medicine 2005, 11: 175-182. PMID: 15685168, DOI: 10.1038/nm1187.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell NucleusCyclin-Dependent Kinase Inhibitor p27Diabetes Mellitus, Type 2Disease Models, AnimalEnzyme InhibitorsHyperglycemiaHyperinsulinismInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansLeptinMiceMice, KnockoutPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, Cell SurfaceReceptors, LeptinSignal TransductionTumor Suppressor ProteinsConceptsCyclin-dependent kinasesInsulin receptor substrate 2Cell cycle progressionPancreatic beta cell proliferationPotential new targetsCompensatory hyperinsulinemiaCycle progressionProtein p27Kip1Substrate 2Type 2 diabetes mellitusPancreatic beta cellsP27Kip1Beta-cell failureBeta-cell proliferationType 2 diabetesLong formNew targetsDeletionDiabetes mellitusDiabetic miceIslet massLeptin receptorBeta cellsAnimal modelsMice