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
2011
IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease
Sadagurski M, Cheng Z, Rozzo A, Palazzolo I, Kelley G, Dong X, Krainc D, White M. IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease. Journal Of Clinical Investigation 2011, 121: 4070-4081. PMID: 21926467, PMCID: PMC3195462, DOI: 10.1172/jci46305.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsBrainDisease Models, AnimalDisease ProgressionFemaleForkhead Box Protein O1Forkhead Transcription FactorsGene ExpressionHumansHuntington DiseaseInsulin Receptor Substrate ProteinsLongevityMaleMiceMice, KnockoutMice, Mutant StrainsMice, TransgenicMitochondriaOxidative StressSignal TransductionConceptsHuntington's diseaseOxidative stressMouse modelProgression of HDMitochondrial dysfunctionMajor risk factorR6/2 mouse modelNeuronal oxidative stressMitochondrial functionHD-like symptomsHD patientsNumber of autophagosomesTranscription factor FOXO1Risk factorsR6/2 miceSlow progressionTherapeutic approachesExpression of IRS2HD progressionLife spanNeurodegenerative diseasesIRS2 levelsProgressionDiseaseMiceRegulation 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
2010
Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1
Wei D, Tao R, Zhang Y, White M, Dong X. Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1. AJP Endocrinology And Metabolism 2010, 300: e312-e320. PMID: 21081708, PMCID: PMC3043623, DOI: 10.1152/ajpendo.00524.2010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedChromatin ImmunoprecipitationDNAFeedback, PhysiologicalForkhead Box Protein O1Forkhead Transcription FactorsGluconeogenesisHepatocytesInsulin Receptor Substrate ProteinsLiverMiceMice, KnockoutPyruvic AcidReceptors, Cytoplasmic and NuclearReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSirtuin 1TransfectionConceptsGene expressionForkhead transcription factor FOXO1PDK4 gene expressionWild-type backgroundChromatin immunoprecipitation analysisProtein deacetylase SIRT1Transcription factor FOXO1Orphan nuclear receptorHepatic gluconeogenesisCatalytic domainDNA sequencesSmall heterodimer partnerImmunoprecipitation analysisInactivation of SIRT1Physiological processesDeacetylase SIRT1Luciferase reporterInsulin receptorFeedback regulationNuclear receptorsFOXO1Heterodimer partnerGenesHepatic insulin receptorSystemic glucose tolerance
2009
Foxo1 integrates insulin signaling with mitochondrial function in the liver
Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers J, Depinho R, Puigserver P, White M. Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nature Medicine 2009, 15: 1307-1311. PMID: 19838201, PMCID: PMC3994712, DOI: 10.1038/nm.2049.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCells, CulturedElectron Transport Chain Complex ProteinsForkhead Box Protein O1Forkhead Transcription FactorsGene Expression RegulationHeme Oxygenase-1HepatocytesInsulinInsulin Receptor Substrate ProteinsLiverMembrane Potential, MitochondrialMembrane ProteinsMiceMice, KnockoutMicroscopy, Electron, TransmissionMitochondriaMutationNADPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaSignal TransductionTrans-ActivatorsTranscription Factors
2008
Inactivation of Hepatic Foxo1 by Insulin Signaling Is Required for Adaptive Nutrient Homeostasis and Endocrine Growth Regulation
Dong X, Copps K, Guo S, Li Y, Kollipara R, DePinho R, White M. Inactivation of Hepatic Foxo1 by Insulin Signaling Is Required for Adaptive Nutrient Homeostasis and Endocrine Growth Regulation. Cell Metabolism 2008, 8: 65-76. PMID: 18590693, PMCID: PMC2929667, DOI: 10.1016/j.cmet.2008.06.006.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsEndocrine GlandsFoodForkhead Transcription FactorsGrowthHomeostasisInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsLiverMiceMice, KnockoutNerve Tissue ProteinsPhosphoproteinsSignal TransductionConceptsInsulin signalingForkhead transcription factor FOXO1Insulin-regulated glucose homeostasisExpression of genesTranscription factor FOXO1Endocrine growth regulationNutrient homeostasisMetabolic genesStress resistancePerturbed expressionActive FoxO1Growth regulationLiver-specific deletionHepatic FoxO1Hepatic insulin resistanceBody sizePI3KHepatic Irs1FOXO1TranscriptomeSomatic growthDKO miceGenesSignalingHomeostasis
2006
The reciprocal stability of FOXO1 and IRS2 creates a regulatory circuit that controls insulin signaling.
Guo S, Dunn S, White M. The reciprocal stability of FOXO1 and IRS2 creates a regulatory circuit that controls insulin signaling. Endocrinology 2006, 20: 3389-99. PMID: 16916938, DOI: 10.1210/me.2006-0092.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedFibroblastsForkhead Box Protein O1Forkhead Transcription FactorsInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, Mutant StrainsPhosphatidylinositol 3-KinasesPhosphoproteinsProtein KinasesProto-Oncogene Proteins c-aktRecombinant ProteinsSignal TransductionTOR Serine-Threonine KinasesTyrosineConceptsInsulin stimulationWild-type mouse embryo fibroblastsInsulin-receptor substrate IRS1Metastatic mammary tumor cellsProlonged insulin stimulationMouse embryo fibroblastsTranscription factor FOXO1Substrates IRS1FoxO phosphorylationRegulatory circuitsNuclear exclusionWT MEFsTyrosine phosphorylationGene expressionMetabolic regulationEmbryo fibroblastsIRS1 expressionMammary tumor cellsIRS2 expressionCell growthIRS2AktIRS1MEFsPancreatic beta cells
2002
The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth
Kitamura T, Nakae J, Kitamura Y, Kido Y, Biggs W, Wright C, White M, Arden K, Accili D. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic β cell growth. Journal Of Clinical Investigation 2002, 110: 1839-1847. PMID: 12488434, PMCID: PMC151657, DOI: 10.1172/jci16857.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell NucleusDiabetes Mellitus, Type 2Epithelial CellsForkhead Box Protein O1Forkhead Transcription FactorsGenes, ReporterHomeodomain ProteinsHumansInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansKidneyMiceMice, KnockoutMicroscopy, FluorescencePancreasPhosphoproteinsPromoter Regions, GeneticProtein IsoformsReceptor, InsulinSignal TransductionTrans-ActivatorsTranscription FactorsConceptsBeta-cell failureBeta-cell proliferationBeta cellsInsulin-producing beta cellsBeta-cell massCell proliferationInsulin receptor substrate 2Pdx1 expressionPancreatic β-cell growthΒ-cell growthTranscription factor FOXO1Pancreatic ductSubset of cellsForkhead transcription factor FOXO1Cell failureNuclear expressionInsulin/IGFRelative deficiencyMutant FoxO1Pdx1 promoterProgenitor cellsFOXO1Gene 1InsulinMice