Featured Publications
BRD7 improves glucose homeostasis independent of IRS proteins.
Kim Y, Lee J, Han Y, Tao R, White M, Liu R, Park S. BRD7 improves glucose homeostasis independent of IRS proteins. Journal Of Endocrinology 2023, 258 PMID: 37578842, PMCID: PMC10430774, DOI: 10.1530/joe-23-0119.Peer-Reviewed Original ResearchConceptsGlucose homeostasisKnockout miceAlternative insulinObese miceGlucose homeostasis independentGlucose metabolism parametersContext of obesityBlood glucose levelsMetabolism parametersGlucose levelsGlucose metabolismInsulinMiceIRS proteinsInsulin receptorProtein 7ObesityHomeostasisUpregulationBRD7InvolvementPathwayNovel insightsEuglycemiaFindings
2021
FoxO1 suppresses Fgf21 during hepatic insulin resistance to impair peripheral glucose utilization and acute cold tolerance
Stöhr O, Tao R, Miao J, Copps K, White M. FoxO1 suppresses Fgf21 during hepatic insulin resistance to impair peripheral glucose utilization and acute cold tolerance. Cell Reports 2021, 34: 108893. PMID: 33761350, PMCID: PMC8529953, DOI: 10.1016/j.celrep.2021.108893.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAdipocytes, BrownAdipose Tissue, BrownAnimalsBlood GlucoseBody WeightCold TemperatureDiet, High-FatFibroblast Growth FactorsForkhead Box Protein O1Gene Expression RegulationGlucoseHomeostasisInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLipid MetabolismLiverMice, KnockoutOrgan SpecificityOxidation-ReductionThermogenesisConceptsHepatic insulin resistanceInsulin resistanceGlucose utilizationHigher plasma Fgf21 levelsSevere hepatic insulin resistanceFGF21 knockout micePlasma FGF21 levelsPeripheral glucose utilizationInsulin-resistant miceThermogenic gene expressionFGF21 resistancePharmacologic formsFGF21 levelsCold intoleranceFGF21 functionMetabolic healthBAT functionGlucose homeostasisKnockout miceFGF21Adenoviral infectionMiceWeight lossSkeletal muscleAcute cold tolerance
2019
Phosphorylation of Forkhead Protein FoxO1 at S253 Regulates Glucose Homeostasis in Mice
Zhang K, Guo X, Yan H, Wu Y, Pan Q, Shen J, Li X, Chen Y, Li L, Qi Y, Xu Z, Xie W, Zhang W, Threadgill D, He L, Villarreal D, Sun Y, White M, Zheng H, Guo S. Phosphorylation of Forkhead Protein FoxO1 at S253 Regulates Glucose Homeostasis in Mice. Endocrinology 2019, 160: 1333-1347. PMID: 30951171, PMCID: PMC6482038, DOI: 10.1210/en.2018-00853.Peer-Reviewed Original ResearchConceptsKey phosphorylation sitesForkhead protein FoxO1Protein kinase BTranscription factor forkhead box O1Factor forkhead box O1FOXO1 nuclear localizationMultiple physiological functionsMouse Foxo1Forkhead box O1Pancreatic plasticityPhosphorylation sitesHuman FOXO1Nuclear localizationTarget genesMolecular basisS253Kinase BFoxO1 activityPhysiological functionsGlucose homeostasisBox O1Pancreatic β-cell functionFOXO1PhosphorylationHepatic glucose production
2018
Inactivating hepatic follistatin alleviates hyperglycemia
Tao R, Wang C, Stöhr O, Qiu W, Hu Y, Miao J, Dong X, Leng S, Stefater M, Stylopoulos N, Lin L, Copps K, White M. Inactivating hepatic follistatin alleviates hyperglycemia. Nature Medicine 2018, 24: 1058-1069. PMID: 29867232, PMCID: PMC6039237, DOI: 10.1038/s41591-018-0048-0.Peer-Reviewed Original ResearchConceptsHepatic glucose productionAdipose tissue insulinGlucose toleranceTissue insulinSuppression of HGPGastric bypass surgeryFed obese miceHepatic insulin resistanceWhite adipose tissuePotential clinical significanceInsulin receptor substrate-1Bypass surgeryGlucose intoleranceHepatic inactivationObese miceInsulin resistanceObese individualsGlycated hemoglobinTranscription factor FOXO1Insulin sensitivityNormal suppressionClinical significanceReceptor substrate-1Adipose tissueExpression of Fst
2013
Phosphatidylcholine Transfer Protein Interacts with Thioesterase Superfamily Member 2 to Attenuate Insulin Signaling
Ersoy B, Tarun A, D’Aquino K, Hancer N, Ukomadu C, White M, Michel T, Manning B, Cohen D. Phosphatidylcholine Transfer Protein Interacts with Thioesterase Superfamily Member 2 to Attenuate Insulin Signaling. Science Signaling 2013, 6: ra64. PMID: 23901139, PMCID: PMC3959124, DOI: 10.1126/scisignal.2004111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGlucoseHEK293 CellsHomeostasisHumansInhibitory Concentration 50InsulinLiverMechanistic Target of Rapamycin Complex 1MiceMice, TransgenicMultiprotein ComplexesPhospholipid Transfer ProteinsPhosphorylationSignal TransductionThiolester HydrolasesTOR Serine-Threonine KinasesTuberous Sclerosis Complex 2 ProteinTumor Suppressor ProteinsConceptsThioesterase superfamily member 2Insulin receptor substrate 2Phosphatidylcholine transfer proteinTSC1-TSC2 complexGenetic ablationRapamycin complex 1Transfer proteinSteady-state amountsMember 2Hepatic glucose homeostasisPhospholipid-binding proteinProtein exhibitInsulin signalingChemical inhibitionKey effectorsSubstrate 2Mammalian targetDiet-induced diabetesProteinTSC2KnockdownGlucose homeostasisPhospholipid-dependent mechanismsActivationComplexes 1Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells*
Geetha T, Rege S, Mathews S, Meakin S, White M, Babu J. Nerve Growth Factor Receptor TrkA, a New Receptor in Insulin Signaling Pathway in PC12 Cells*. Journal Of Biological Chemistry 2013, 288: 23807-23813. PMID: 23749991, PMCID: PMC3745327, DOI: 10.1074/jbc.m112.436279.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsEnzyme ActivationGlucoseHumansInsulinInsulin Receptor Substrate ProteinsMitogen-Activated Protein Kinase 7Molecular Sequence DataNerve Growth FactorPC12 CellsPhosphorylationPhosphotyrosineProtein BindingProto-Oncogene Proteins c-aktRatsReceptor, InsulinReceptor, trkASignal TransductionConceptsInsulin receptor substrate-1Insulin receptorPC12 cellsTrkA kinase domainTransmembrane receptor tyrosine kinaseKinase-inactive mutantInsulin Signaling PathwayReceptor substrate-1Nerve growth factor receptor TrkAReceptor tyrosine kinasesNerve growth factorActivation of AktNPXY motifKinase domainTyrosine phosphorylationSubstrate-1Regulatory loopTyrosine kinaseSignaling pathwaysGrowth factorNew receptorsReceptor TrkACellsPathwayTrkA
2012
IRS2 Signaling in LepR-b Neurons Suppresses FoxO1 to Control Energy Balance Independently of Leptin Action
Sadagurski M, Leshan R, Patterson C, Rozzo A, Kuznetsova A, Skorupski J, Jones J, Depinho R, Myers M, White M. IRS2 Signaling in LepR-b Neurons Suppresses FoxO1 to Control Energy Balance Independently of Leptin Action. Cell Metabolism 2012, 15: 703-712. PMID: 22560222, PMCID: PMC3361909, DOI: 10.1016/j.cmet.2012.04.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCytoskeletal ProteinsEnergy MetabolismFemaleForkhead Box Protein O1Forkhead Transcription FactorsGene ExpressionGlucoseGlucose IntoleranceHomeostasisInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLeptinMaleMiceMice, TransgenicNerve Tissue ProteinsNeuronsObesityReceptors, LeptinSignal TransductionConceptsLeptin actionGlucose homeostasisGlucose intoleranceInsulin resistanceHormone leptinFoxO1 nuclear exclusionIRS2 expressionLeptin receptorMetabolic actionsNeuronsMiceEnergy balanceFOXO1Metabolic sensingIRS2HomeostasisGene expressionNuclear exclusionObesityLeptinExpressionCNSInsulinIntoleranceBrain
2011
Regulation of glucose homeostasis through a XBP-1–FoxO1 interaction
Zhou Y, Lee J, Reno C, Sun C, Park S, Chung J, Lee J, Fisher S, White M, Biddinger S, Ozcan U. Regulation of glucose homeostasis through a XBP-1–FoxO1 interaction. Nature Medicine 2011, 17: 356-365. PMID: 21317886, PMCID: PMC3897616, DOI: 10.1038/nm.2293.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseDisease Models, AnimalDNA-Binding ProteinsForkhead Box Protein O1Forkhead Transcription FactorsGlucoseHomeostasisHydrolysisInsulin ResistanceLiverMiceMutationPhosphorylationReceptor, InsulinRegulatory Factor X Transcription FactorsSignal TransductionTranscription FactorsX-Box Binding Protein 1Insulin Receptor Substrates Irs1 and Irs2 Coordinate Skeletal Muscle Growth and Metabolism via the Akt and AMPK Pathways
Long Y, Cheng Z, Copps K, White M. Insulin Receptor Substrates Irs1 and Irs2 Coordinate Skeletal Muscle Growth and Metabolism via the Akt and AMPK Pathways. Molecular And Cellular Biology 2011, 31: 430-441. PMID: 21135130, PMCID: PMC3028618, DOI: 10.1128/mcb.00983-10.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsBody CompositionBody WeightEnzyme ActivationForkhead Transcription FactorsGlucoseHomeostasisIn Vitro TechniquesInsulinInsulin Receptor Substrate ProteinsLactic AcidMiceMice, KnockoutModels, BiologicalMuscle, SkeletalMyocardiumOrgan SizeOrgan SpecificityProto-Oncogene Proteins c-aktSignal TransductionUp-RegulationConceptsSkeletal muscle growthMdKO miceMuscle growthElevated AMP/ATP ratioInsulin-receptor substrate IRS1AMP/ATP ratioSkeletal muscleInsulin receptor substrateMuscle creatine kinaseSubstrates IRS1Insulin-stimulated glucose uptakeProtein kinaseNutrient availabilityReceptor substrateCarboxylase phosphorylationFatty acid oxidationAMPK pathwayMetabolic homeostasisATP ratioIRS1Impaired growthKinaseAmino acid releaseSkeletal muscle massAtrogene expression
2009
Human IL6 enhances leptin action in mice
Sadagurski M, Norquay L, Farhang J, D’Aquino K, Copps K, White M. Human IL6 enhances leptin action in mice. Diabetologia 2009, 53: 525-535. PMID: 19902173, PMCID: PMC2815798, DOI: 10.1007/s00125-009-1580-8.Peer-Reviewed Original ResearchConceptsOb/ob miceWild-type miceOb miceHuman IL6Leptin actionDiet-induced obesityHigh-fat dietLower leptin concentrationsHypothalamic signal transducerCentral leptin actionSystemic inflammationTranscription 3 (STAT3) phosphorylationLeptin injectionInflammatory cytokinesInsulin resistanceLeptin concentrationsFood intakePhysical activityGlucose homeostasisAims/Body weightIL6MiceEnergy expenditureObesityThe Irs1 Branch of the Insulin Signaling Cascade Plays a Dominant Role in Hepatic Nutrient Homeostasis
Guo S, Copps K, Dong X, Park S, Cheng Z, Pocai A, Rossetti L, Sajan M, Farese R, White M. The Irs1 Branch of the Insulin Signaling Cascade Plays a Dominant Role in Hepatic Nutrient Homeostasis. Molecular And Cellular Biology 2009, 29: 5070-5083. PMID: 19596788, PMCID: PMC2738277, DOI: 10.1128/mcb.00138-09.Peer-Reviewed Original ResearchConceptsHigh-fat dietHepatic nutrient homeostasisIntracerebroventricular insulin infusionSuppression of HGPImpaired glucose toleranceHyperinsulinemic-euglycemic clampHepatic insulin actionHepatic glucose productionHepatic Irs1Cre-loxP approachLivers of controlGlucose toleranceInsulin infusionInsulin Signaling CascadeInsulin sensitivityPostprandial hyperglycemiaGlucose homeostasisInsulin actionPrincipal mediatorGlucose productionLipogenic genesMiceTyrosine phosphorylationLiverIRS2Insulin 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 injectionTargeted Disruption of ROCK1 Causes Insulin Resistance in Vivo *
Lee D, Shi J, Jeoung N, Kim M, Zabolotny J, Lee S, White M, Wei L, Kim Y. Targeted Disruption of ROCK1 Causes Insulin Resistance in Vivo *. Journal Of Biological Chemistry 2009, 284: 11776-11780. PMID: 19276091, PMCID: PMC2673246, DOI: 10.1074/jbc.c900014200.Peer-Reviewed Original ResearchMeSH KeywordsAdiposityAnimalsDiabetes Mellitus, Type 2GlucoseGTPase-Activating ProteinsInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceMiceMice, KnockoutObesityPhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktRho-Associated KinasesRibosomal Protein S6 KinasesSignal TransductionConceptsIRS-1Skeletal muscleWhole-body glucose homeostasisInsulin resistanceBody glucose homeostasisCultured cell linesPhosphorylation of AktPhospho-tyrosinesGlucose homeostasisROCK1-deficient miceSerine phosphorylationNovel regulatorTyrosine phosphorylationS6KRho kinase isoformsInsulin sensitivityPhysiological roleGene ablationAbility of insulinInsulin receptorTargeted disruptionPhosphorylationNormal glucose homeostasisGlucose-induced insulin secretionROCK1Breathing Room: The (Un)Natural History of Adipose Microhypoxia and Insulin Resistance
Copps K, White M. Breathing Room: The (Un)Natural History of Adipose Microhypoxia and Insulin Resistance. Diabetes 2009, 58: 26-27. PMID: 19114728, PMCID: PMC2606882, DOI: 10.2337/db08-1517.Peer-Reviewed Original Research
2007
Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis
Taguchi A, Wartschow L, White M. Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis. Science 2007, 317: 369-372. PMID: 17641201, DOI: 10.1126/science.1142179.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsBrainCircadian RhythmCrosses, GeneticDietFemaleGlucoseHomeostasisInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLongevityMaleMiceMice, KnockoutMice, TransgenicOverweightOxidation-ReductionOxygen ConsumptionPhosphoproteinsRespirationSignal TransductionSuperoxide Dismutase
2005
Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth
Dong X, Park S, Lin X, Copps K, Yi X, White M. Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth. Journal Of Clinical Investigation 2005, 116: 101-114. PMID: 16374520, PMCID: PMC1319221, DOI: 10.1172/jci25735.Peer-Reviewed Original ResearchConceptsSystemic growthHundreds of genesInsulin receptor substrateHepatic nutrient homeostasisHepatic glucose homeostasisHeterologous pathwaysNutrient homeostasisReceptor substrateGene expressionGSK3beta phosphorylationReceptor signalsHepatic gene expressionLKO miceInsulin receptorGlucose homeostasisIRS2IRS1Hepatic genesHepatic insulin receptorAkt-FoxO1 pathwayHomeostasisGenesHepatic glycogen storesLKO liversPathwayExendin-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 insulinPhosphatidylinositolTolerancePhosphorylationMiceSignalingHomeostasisInsulin Receptor Substrate 2 Plays Diverse Cell-specific Roles in the Regulation of Glucose Transport*
Sadagurski M, Weingarten G, Rhodes C, White M, Wertheimer E. Insulin Receptor Substrate 2 Plays Diverse Cell-specific Roles in the Regulation of Glucose Transport*. Journal Of Biological Chemistry 2005, 280: 14536-14544. PMID: 15705592, DOI: 10.1074/jbc.m410227200.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBiological TransportDeoxyglucoseEpidermisFibroblastsGenotypeGlucoseHomozygoteImmunoblottingImmunoprecipitationInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsKeratinocytesMiceMice, KnockoutPhosphatidylinositol 3-KinasesPhosphoproteinsSkinThymidineTime FactorsConceptsIRS-2Glucose transportInsulin receptor substrate-2 proteinInsulin-induced glucose transportInsulin receptor substrate 2Insulin-stimulated glucose transportIRS-1 proteinCell specific associationIRS-2 proteinClassical insulin target tissuesCell-specific mannerSkin epidermal keratinocytesIRS-PICell-specific rolePositive regulatorInsulin target tissuesCell physiologyDermal fibroblastsKO cellsEpidermal keratinocytesAkt activationPhosphatidylinositolSubstrate 2Insulin receptorProtein
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 failureCells