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
RIP-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 ResearchMeSH KeywordsAnimalsFemaleGene TargetingGlucose IntoleranceInsulinInsulin-Secreting CellsIntegrasesMaleMiceMice, TransgenicPromoter Regions, GeneticRatsConceptsRIP-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
2003
cAMP promotes pancreatic β-cell survival via CREB-mediated induction of IRS2
Jhala U, Canettieri G, Screaton R, Kulkarni R, Krajewski S, Reed J, Walker J, Lin X, White M, Montminy M. cAMP promotes pancreatic β-cell survival via CREB-mediated induction of IRS2. Genes & Development 2003, 17: 1575-1580. PMID: 12842910, PMCID: PMC196130, DOI: 10.1101/gad.1097103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell LineCell SurvivalColforsinCyclic AMPCyclic AMP Response Element-Binding ProteinDiabetes MellitusGene Expression RegulationGlucagonGlucagon-Like Peptide 1GlucoseGlucose IntoleranceHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansMiceMice, TransgenicPeptide FragmentsPhosphoproteinsPhosphorylationPromoter Regions, GeneticProtein PrecursorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionTransfectionTransgenesTumor Cells, CulturedConceptsPancreatic β-cell survivalActivity of CREBSecond messenger cAMPSurvival kinase AktΒ-cell survivalKinase AktPathway componentsA-CREBCREB actionExpression of IRS2Cell survivalBeta-cell apoptosisDirect targetIslet cell survivalNovel mechanismCREBIRS2ExpressionCAMPInductionTransgeneAktIGF-1ApoptosisSurvival
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 1InsulinMiceInterleukin-4-mediated Protection of Primary B Cells from Apoptosis through Stat6-dependent Up-regulation of Bcl-xL*
Wurster A, Rodgers V, White M, Rothstein T, Grusby M. Interleukin-4-mediated Protection of Primary B Cells from Apoptosis through Stat6-dependent Up-regulation of Bcl-xL*. Journal Of Biological Chemistry 2002, 277: 27169-27175. PMID: 12023955, DOI: 10.1074/jbc.m201207200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-X ProteinBlotting, NorthernB-LymphocytesCell DeathCells, CulturedImmunoblottingInterleukin-4LuciferasesLymphocytesMicePromoter Regions, GeneticPropidiumProtein BindingProto-Oncogene Proteins c-bcl-2RetroviridaeSignal TransductionSTAT6 Transcription FactorTime FactorsTrans-ActivatorsTranscription, GeneticTransfectionUp-RegulationConceptsFas-induced cell deathIL-4B cellsPrimary B cellsBcl-xLCell deathBcl-2 family membersBcl-xL transcriptionB lymphocyte developmentB lymphocyte apoptosisSTAT6-dependent mannerAnti-apoptotic cytokinesActivation of STAT6Splenic B cellsAnti-apoptotic activityIL-4 stimulationInterleukin-4Lymphocyte apoptosisBcl-xL.B lymphocytesMolecular eventsSubsequent transcriptionCytokine receptorsLymphocyte developmentCell survival
1999
Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of their relation with alterations in insulin secretion and insulin sensitivity
Almind K, Frederiksen S, Bernal D, Hansen T, Ambye L, Urhammer S, Ekstrøm C, Berglund L, Reneland R, Lithell H, White M, Van Obberghen E, Pedersen O. Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of their relation with alterations in insulin secretion and insulin sensitivity. Diabetologia 1999, 42: 1244-1249. PMID: 10525667, DOI: 10.1007/s001250051299.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAmino Acid SubstitutionBase SequenceDiabetes Mellitus, Type 2Gene FrequencyGenetic Carrier ScreeningGenetic TestingGlucose Tolerance TestHumansInsulinInsulin Receptor Substrate ProteinsInsulin SecretionIntracellular Signaling Peptides and ProteinsMaleMiddle AgedMolecular Sequence DataPedigreePhosphoproteinsPhosphotyrosinePolymorphism, Single-Stranded ConformationalPromoter Regions, GeneticProspective StudiesTwo-Hybrid System TechniquesConceptsType II diabetic patientsII diabetic patientsSerum insulin concentrationsInsulin secretionDiabetic patientsInsulin sensitivityInsulin concentrationsGly1057Asp variantInsulin receptor substrate-2 (IRS-2) geneIntravenous glucose tolerance testGlucose-tolerant offspringGlucose tolerance testGlucose-tolerant subjectsIRS-2Elderly Swedish menMiddle-aged subjectsYoung healthy subjectsAmino acid variantsWildtype carriersDiabetic parentsTolerance testTolerant subjectsHealthy subjectsStudy groupInsulin sensivity