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 insightsEuglycemiaFindingsTAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
Xu S, Liu Y, Hu R, Wang M, Stöhr O, Xiong Y, Chen L, Kang H, Zheng L, Cai S, He L, Wang C, Copps K, White M, Miao J. TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states. ELife 2021, 10: e57462. PMID: 34622775, PMCID: PMC8555985, DOI: 10.7554/elife.57462.Peer-Reviewed Original ResearchConceptsGluconeogenic gene promotersBinding of GRGene promoterGlucocorticoid receptorGlucose homeostasisLigand-binding domainGlucose productionOverexpression of TAZHepatic glucose homeostasisWW domainsBlood glucose concentrationPhysiological fastingGluconeogenic genesGR response elementResponse elementNovel roleTAZNormal physiological stateGR transactivationPhysiological statePromoterMouse liverPericentral hepatocytesPathological statesGlucose concentration
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
2016
Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice
Kuznetsova A, Yu Y, Hollister-Lock J, Opare-Addo L, Rozzo A, Sadagurski M, Norquay L, Reed J, Khattabi I, Bonner-Weir S, Weir G, Sharma A, White M. Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice. JCI Insight 2016, 1: e80749. PMID: 27152363, PMCID: PMC4854304, DOI: 10.1172/jci.insight.80749.Peer-Reviewed Original ResearchInsulin receptor substrate 2Progression of diabetesΒ-cell growthHuman isletsΒ-cellsHuman islet transplantsIsolated human pancreatic isletsAdverse systemic effectsFirst-generation antihistaminesHistamine H1 receptorsΒ-cell replicationPancreatic β-cell growthAnti-CD3 AbPancreatic β-cellsHuman pancreatic isletsNuclear Pdx1NOD miceIslet transplantsDiabetic miceCell growthH1 receptorsIslet massIRS2 expressionDownstream signaling cascadesGlucose homeostasis
2013
Irs2 and Irs4 synergize in non-LepRb neurons to control energy balance and glucose homeostasis
Sadagurski M, Dong X, Myers M, White M. Irs2 and Irs4 synergize in non-LepRb neurons to control energy balance and glucose homeostasis. Molecular Metabolism 2013, 3: 55-63. PMID: 24567904, PMCID: PMC3929908, DOI: 10.1016/j.molmet.2013.10.004.Peer-Reviewed Original ResearchFed blood glucose levelsBlood glucose levelsLepRb neuronsSevere obesityInsulin resistanceInsulin receptor substrateGlucose levelsLeptin receptorGlucose homeostasisBody weightInsulin/IGF1MiceMetabolic homeostasisEnergy expenditureNeuronsWhole bodyReceptor substrateIRS2Metabolic sensingHomeostasisMetabolic regulationHyperglycemiaLepRbObesityHypothalamusPhosphatidylcholine 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 1Chronic 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
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 1
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 phosphorylationLiverIRS2The 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 homeostasisTargeted 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 secretionROCK1
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 ResearchThe Relationship Between the Insulin Receptor Substrates and Metabolic Disease
White M. The Relationship Between the Insulin Receptor Substrates and Metabolic Disease. Contemporary Endocrinology 2008, 255-278. DOI: 10.1007/978-1-60327-116-5_14.Peer-Reviewed Original Research
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 liversPathwayPhosphatase 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 insulinPhosphatidylinositolTolerancePhosphorylationMiceSignalingHomeostasisCyclins 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
Disruption of the SH2-B Gene Causes Age-Dependent Insulin Resistance and Glucose Intolerance
Duan C, Yang H, White M, Rui L. Disruption of the SH2-B Gene Causes Age-Dependent Insulin Resistance and Glucose Intolerance. Molecular And Cellular Biology 2004, 24: 7435-7443. PMID: 15314154, PMCID: PMC506995, DOI: 10.1128/mcb.24.17.7435-7443.2004.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdipose TissueAgingAnimalsBlood GlucoseCarrier ProteinsCell LineDietary FatsGlucose IntoleranceHomeostasisHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansLiverMaleMiceMice, Inbred StrainsMice, KnockoutMitogen-Activated Protein KinasesMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionConceptsSrc homology 2Insulin receptor substrate-1Insulin receptor activationInsulin receptorTyrosine phosphorylationSH2 domain-dependent mannerPleckstrin homology domain-containing adaptor proteinDomain-containing adaptor proteinDomain-dependent mannerReceptor substrate-1Skeletal muscleSH2 domainHomology 2Adaptor proteinReceptor activationSubstrate-1Physiological roleCultured cellsGlucose homeostasisERK1/2 pathwayDependent insulin resistancePhysiological enhancerSystemic deletionPhosphorylationIRS2