2018
Insulin signaling and reduced glucocorticoid receptor activity attenuate postprandial gene expression in liver
Kalvisa A, Siersbæk M, Præstholm S, Christensen L, Nielsen R, Stohr O, Vettorazzi S, Tuckermann J, White M, Mandrup S, Grøntved L. Insulin signaling and reduced glucocorticoid receptor activity attenuate postprandial gene expression in liver. PLOS Biology 2018, 16: e2006249. PMID: 30532187, PMCID: PMC6301715, DOI: 10.1371/journal.pbio.2006249.Peer-Reviewed Original ResearchConceptsCircadian gene transcriptionGene transcriptionGene expressionCircadian-regulated genesInsulin-regulated genesGenomic approachesGlucocorticoid receptorGene programEnhancer activityCistromic analysisGlucocorticoid receptor activityGenesMechanistic insightsTranscriptionFeeding behaviorSelective disruptionDiet-induced obese animalsEnhancerReceptor activityFeeding responseDiet-induced obesityExpressionDysregulationChromatinFOXO1
2016
Mechanism of Insulin Action
White M. Mechanism of Insulin Action. 2016, 114-132. DOI: 10.1002/9781118924853.ch8.Peer-Reviewed Original ResearchInsulin-like signalingGenome-wide association studiesInsulin-like peptidesClassical insulin target tissuesInsulin-like growth factor 2Receptor tyrosine kinasesSimilar receptor tyrosine kinasesEnvironmental signalsHuman genomeInsulin target tissuesGenetic lociPancreatic β-cellsInsulin signalTyrosine kinaseAssociation studiesRelease of nutrientsConflicting signalsGrowth factor 2IGF signalingAnimal growthFactor 1Factor 2Insulin-like growth factor-1Β-cellsGenes
2013
Genetic Inactivation of Pyruvate Dehydrogenase Kinases Improves Hepatic Insulin Resistance Induced Diabetes
Tao R, Xiong X, Harris R, White M, Dong X. Genetic Inactivation of Pyruvate Dehydrogenase Kinases Improves Hepatic Insulin Resistance Induced Diabetes. PLOS ONE 2013, 8: e71997. PMID: 23940800, PMCID: PMC3733847, DOI: 10.1371/journal.pone.0071997.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, ExperimentalGene Expression Regulation, EnzymologicGene SilencingGlucose IntoleranceGlucose Tolerance TestInsulin Receptor Substrate ProteinsInsulin ResistanceLiverMiceMice, KnockoutOrgan SpecificityProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring KinaseConceptsPyruvate dehydrogenase kinasePDK4 geneGene knockdownDehydrogenase kinasePDK4 gene expressionMitochondrial pyruvate dehydrogenasePdk geneGene attributesPDK2 genesGene inactivationGene expressionGenetic inactivationPyruvate dehydrogenaseGenesInsulin receptorMetabolic analysisSpecific shRNAGene deletionGenetic backgroundHepatic insulin receptorNull miceKinasePDK2KnockdownCritical role
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
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
2007
The Repression of IRS2 Gene by ATF3, a Stress-Inducible Gene, Contributes to Pancreatic β-Cell Apoptosis
Li D, Yin X, Zmuda E, Wolford C, Dong X, White M, Hai T. The Repression of IRS2 Gene by ATF3, a Stress-Inducible Gene, Contributes to Pancreatic β-Cell Apoptosis. Diabetes 2007, 57: 635-644. PMID: 18057093, DOI: 10.2337/db07-0717.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 3AnimalsApoptosisCell LineCells, CulturedDown-RegulationInsulinInsulin Receptor Substrate ProteinsInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutPhosphoproteinsPromoter Regions, GeneticRatsStress, PhysiologicalTime FactorsConceptsStress-inducible genesIRS2 gene expressionIRS2 promoterBinding of ATF3Gene transcriptionGene expressionExpression of IRS2Chromatin immunoprecipitation assaysIRS2 genePancreatic β-cell apoptosisEnvironmental stress factorsΒ-cell apoptosisTranscription factor 3Effect of ATF3Stress signalsImmunoprecipitation assaysBeta-cell survivalTarget genesProapoptotic genesExpression of ATF3GenesTranscriptionIRS2 expressionATF3Promoter
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 liversPathwayRIP-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 systemSecretion
1998
Mapping of the human insulin receptor substrate-2 gene, identification of a linked polymorphic marker and linkage analysis in families with Type II diabetes: no evidence for a major susceptibility role
Kalidas K, Wasson J, Glaser B, Meyer J, Duprat L, White M, Permutt M. Mapping of the human insulin receptor substrate-2 gene, identification of a linked polymorphic marker and linkage analysis in families with Type II diabetes: no evidence for a major susceptibility role. Diabetologia 1998, 41: 1389-1391. PMID: 9833949, DOI: 10.1007/s001250051081.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceChromosome MappingChromosomes, Human, Pair 13Diabetes Mellitus, Type 1Europe, EasternGenetic Carrier ScreeningGenetic LinkageGenetic MarkersGenotypeHumansInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsJewsMiceMicrosatellite RepeatsPhosphoproteinsPolymorphism, GeneticStatistics, NonparametricConceptsIRS-2 geneRadiation hybrid panel mappingPolymorphic markersInsulin receptor substrate 2Nonparametric linkage analysisMap positionChromosome 13q34Evidence of linkageInsulin receptor substrate-2 (IRS-2) geneGene regionLinkage analysisGenesSubstrate 2Excess alleleInsulin receptorNearby markersType II diabetesAshkenazi Jewish familiesMice resultsII diabetesSusceptibility roleMarkersFamilyPeripheral insulin resistance