2008
Genetic Deficiency of Glycogen Synthase Kinase-3β Corrects Diabetes in Mouse Models of Insulin Resistance
Tanabe K, Liu Z, Patel S, Doble B, Li L, Cras-Méneur C, Martinez S, Welling C, White M, Bernal-Mizrachi E, Woodgett J, Permutt M. Genetic Deficiency of Glycogen Synthase Kinase-3β Corrects Diabetes in Mouse Models of Insulin Resistance. PLOS Biology 2008, 6: e37. PMID: 18288891, PMCID: PMC2245985, DOI: 10.1371/journal.pbio.0060037.Peer-Reviewed Original ResearchConceptsBeta-cell massIrs2-/- miceInsulin resistanceMouse modelType 2 diabetes mellitusObese insulin-resistant individualsWhole-body glucose disposalOnset of diabetesPdx1 levelsBeta-cell functionBeta-cell lossInsulin-resistant individualsBeta-cell replicationGSK-3betaBeta-cell proliferationInsulin receptor substrate 2Cyclin-dependent kinase inhibitorDiabetes mellitusDiabetes onsetEarly diabetesPI-3K/Akt pathwayGlucose disposalGSK-3beta activityDiabetesInsulin action
2005
Cyclins 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 developmentAlterations in growth and apoptosis of insulin receptor substrate-1-deficient β-cells
Hennige A, Ozcan U, Okada T, Jhala U, Schubert M, White M, Kulkarni R. Alterations in growth and apoptosis of insulin receptor substrate-1-deficient β-cells. AJP Endocrinology And Metabolism 2005, 289: e337-e346. PMID: 15827066, DOI: 10.1152/ajpendo.00032.2004.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsApoptosisCell ProliferationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceIntracellular Signaling Peptides and ProteinsIslets of LangerhansIslets of Langerhans TransplantationKidneyMaleMiceMice, Inbred C57BLMice, KnockoutPhosphoproteinsSignal TransductionConceptsInsulin resistanceInsulin receptor substrateWT recipientsInsulin/IGFIRS-1 knockout miceBeta-cell proliferationBeta-cell apoptosisIslet hypoplasiaIRS-2 expressionEndogenous isletsOvert diabetesKidney capsuleIslet responseIslet functionIslet defectKnockout miceMitotic rateCompensatory increaseIslet growthDysfunctional isletsGrowth retardationTransplantation approachesΒ-cellsAntiapoptotic effectIGFDeletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice
Uchida T, Nakamura T, Hashimoto N, Matsuda T, Kotani K, Sakaue H, Kido Y, Hayashi Y, Nakayama K, White M, Kasuga M. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nature Medicine 2005, 11: 175-182. PMID: 15685168, DOI: 10.1038/nm1187.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell NucleusCyclin-Dependent Kinase Inhibitor p27Diabetes Mellitus, Type 2Disease Models, AnimalEnzyme InhibitorsHyperglycemiaHyperinsulinismInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansLeptinMiceMice, KnockoutPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, Cell SurfaceReceptors, LeptinSignal TransductionTumor Suppressor ProteinsConceptsCyclin-dependent kinasesInsulin receptor substrate 2Cell cycle progressionPancreatic beta cell proliferationPotential new targetsCompensatory hyperinsulinemiaCycle progressionProtein p27Kip1Substrate 2Type 2 diabetes mellitusPancreatic beta cellsP27Kip1Beta-cell failureBeta-cell proliferationType 2 diabetesLong formNew targetsDeletionDiabetes mellitusDiabetic miceIslet massLeptin receptorBeta cellsAnimal modelsMice
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 1InsulinMiceDefective insulin secretion in pancreatic β cells lacking type 1 IGF receptor
Xuan S, Kitamura T, Nakae J, Politi K, Kido Y, Fisher P, Morroni M, Cinti S, White M, Herrera P, Accili D, Efstratiadis A. Defective insulin secretion in pancreatic β cells lacking type 1 IGF receptor. Journal Of Clinical Investigation 2002, 110: 1011-1019. PMID: 12370279, PMCID: PMC151144, DOI: 10.1172/jci15276.Peer-Reviewed Original ResearchConceptsType 1 IGF receptorBeta-cell massDefective insulin secretionInsulin secretionIGF receptorInsulin releaseInadequate compensatory increaseGlucose-dependent insulin releaseBeta-cell proliferationAge-dependent impairmentPancreatic β-cellsGlucose toleranceDecrease of glucoseBeta cellsType 2Compensatory increaseCell massΒ-cellsReceptor tyrosine kinasesSecretionCell proliferationAntiapoptotic roleReceptorsTyrosine kinaseConditional mutagenesis
1999
Stimulation of pancreatic beta-cell proliferation by growth hormone is glucose-dependent: signal transduction via janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) with no crosstalk to insulin receptor substrate-mediated mitogenic signalling.
Cousin S, Hügl S, Myers M, White M, Reifel-Miller A, Rhodes C. Stimulation of pancreatic beta-cell proliferation by growth hormone is glucose-dependent: signal transduction via janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) with no crosstalk to insulin receptor substrate-mediated mitogenic signalling. Biochemical Journal 1999, 344 Pt 3: 649-58. PMID: 10585851, PMCID: PMC1220686, DOI: 10.1042/0264-6021:3440649.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAnimalsCell DivisionCell LineDNA-Binding ProteinsGlucoseGRB2 Adaptor ProteinGrowth HormoneInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansJanus Kinase 2Milk ProteinsMitogen-Activated Protein KinasesPhosphoproteinsPhosphorylationProteinsProtein-Tyrosine KinasesProto-Oncogene ProteinsRatsRibosomal Protein S6 KinasesShc Signaling Adaptor ProteinsSignal TransductionSon of Sevenless Protein, DrosophilaSrc Homology 2 Domain-Containing, Transforming Protein 1STAT5 Transcription FactorTrans-ActivatorsConceptsINS-1 cell proliferationSignal transduction pathwaysSignal transductionCell proliferationKinase 2Sevenless-1 proteinMitogenic signal transduction pathwaysJAK2/STAT5 pathwayMitogen-activated protein kinaseInsulin receptor substrateBeta-cell proliferationRat growth hormoneJAK2/STAT5Pancreatic beta cell proliferationMitogenic signalingS6 kinaseProtein kinaseProtein associationTranscription 5Beta-cell lineReceptor substrateDifferent mitogenicRat beta-cell lineDownstream activationIRS-2
1998
Insulin-like Growth Factor I (IGF-I)-stimulated Pancreatic β-Cell Growth Is Glucose-dependent SYNERGISTIC ACTIVATION OF INSULIN RECEPTOR SUBSTRATE-MEDIATED SIGNAL TRANSDUCTION PATHWAYS BY GLUCOSE AND IGF-I IN INS-1 CELLS*
Hügl S, White M, Rhodes C. Insulin-like Growth Factor I (IGF-I)-stimulated Pancreatic β-Cell Growth Is Glucose-dependent SYNERGISTIC ACTIVATION OF INSULIN RECEPTOR SUBSTRATE-MEDIATED SIGNAL TRANSDUCTION PATHWAYS BY GLUCOSE AND IGF-I IN INS-1 CELLS*. Journal Of Biological Chemistry 1998, 273: 17771-17779. PMID: 9651378, DOI: 10.1074/jbc.273.28.17771.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor IGrowth factor IBeta-cell proliferationINS-1 cell proliferationCell proliferationFactor IMM glucoseCombination of IGFPancreatic β-cell growthPancreatic beta-cell lineBeta-cell lineΒ-cell growthINS-1 cellsNM IGFBeta-cell mitogenesisCertain growth factorsSignaling mechanismSignal transduction pathwaysGlucose metabolismIGFCell proliferation rateGrowth factorIRS-2Transduction pathwaysGlucose concentration