2003
Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes
Hennige A, Burks D, Ozcan U, Kulkarni R, Ye J, Park S, Schubert M, Fisher T, Dow M, Leshan R, Zakaria M, Mossa-Basha M, White M. Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes. Journal Of Clinical Investigation 2003, 112: 1521-1532. PMID: 14617753, PMCID: PMC259126, DOI: 10.1172/jci18581.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell SizeDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Dietary FatsGene Expression RegulationHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsIslets of LangerhansIslets of Langerhans TransplantationMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPhosphoproteinsReceptor, InsulinSignal TransductionSurvival RateUp-RegulationConceptsPancreatic beta-cell functionPeripheral insulin actionBeta-cell failureBeta-cell functionType 2 diabetesIrs2-/- miceInsulin receptor substrate 2Beta-cell growthBeta cell-specific expressionPrevents diabetesObese miceTransgenic isletsInsulin secretionWT isletsIRS2 expressionPharmacological approachesBeta cellsPhysiologic responsesInsulin actionRational treatmentDiabetesInsulin/IGFCell functionMiceCell-specific expressionInsulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation
Schubert M, Brazil D, Burks D, Kushner J, Ye J, Flint C, Farhang-Fallah J, Dikkes P, Warot X, Rio C, Corfas G, White M. Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation. Journal Of Neuroscience 2003, 23: 7084-7092. PMID: 12904469, PMCID: PMC6740672, DOI: 10.1523/jneurosci.23-18-07084.2003.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsApoptosisBody WeightBrainCell CountCell DivisionCell SurvivalCells, CulturedCerebellumCrosses, GeneticEnzyme InhibitorsHeterozygoteIn Situ Nick-End LabelingInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutNeuronsOrgan SizePhosphoproteinsPhosphorylationReceptor, IGF Type 1Signal TransductionTau ProteinsConceptsMolecular linkInsulin receptor substrate (IRS) proteinsBrain growthNeurodegenerative diseasesPancreatic beta-cell functionPeripheral insulin actionSubstrate proteinsBeta-cell functionTyrosine phosphorylationLike growth factorIrs2 branchInsulin resistanceTau phosphorylationIRS2 geneNeuronal proliferationInsulin actionMouse brainInsulin-IGFGrowth factorPhosphorylationIRS2DiabetesBody growthDiseaseMiceChapter 72 IRS-Protein Scaffolds and Insulin/IGF Action
White M. Chapter 72 IRS-Protein Scaffolds and Insulin/IGF Action. 2003, 409-419. DOI: 10.1016/b978-012124546-7/50433-2.Peer-Reviewed Original ResearchIRS protein familyMultiple biological processesIRS proteinsIL-9 signalingTissue agingBiological processesIRS-2Growth controlPeripheral insulin sensitivityPeripheral insulin actionType 2 diabetesPancreatic p-cellsCell functionIRS2IGF actionIL-4Insulin sensitivityInflammatory responseInsulin actionInsulin secretionIL-7Immune responseFundamental roleTumor growthP cells
2002
Pdx1 restores β cell function in Irs2 knockout mice
Kushner J, Ye J, Schubert M, Burks D, Dow M, Flint C, Dutta S, Wright C, Montminy M, White M. Pdx1 restores β cell function in Irs2 knockout mice. Journal Of Clinical Investigation 2002, 109: 1193-1201. PMID: 11994408, PMCID: PMC150960, DOI: 10.1172/jci14439.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBlood GlucoseBody WeightDiabetes Mellitus, Type 2FemaleHomeodomain ProteinsInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsIslets of LangerhansMaleMiceMice, KnockoutPhosphoproteinsReceptor, InsulinSignal TransductionTrans-ActivatorsConceptsOnset of diabetesPeripheral insulin actionBeta-cell failureType 2 diabetesBeta-cell massEarly-onset diabetesIrs2 knockout micePancreatic beta-cell growthBeta-cell growthWeeks of ageIrs2 branchHepatocyte nuclear factorGlucose toleranceExpression of Pdx1Knockout miceBeta cellsDiabetesInsulin actionInsulin/MiceNuclear factorTranscription factor Pdx1Cell functionIsletsTransgenic expression
2001
Regulation of Insulin/Insulin-like Growth Factor-1 Signaling by Proteasome-mediated Degradation of Insulin Receptor Substrate-2*
Rui L, Fisher T, Thomas J, White M. Regulation of Insulin/Insulin-like Growth Factor-1 Signaling by Proteasome-mediated Degradation of Insulin Receptor Substrate-2*. Journal Of Biological Chemistry 2001, 276: 40362-40367. PMID: 11546773, DOI: 10.1074/jbc.m105332200.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsCarcinoma, HepatocellularDiabetes Mellitus, Type 2Down-RegulationFeedbackFibroblastsHumansInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsLiver Neoplasms, ExperimentalMiceMitogen-Activated Protein KinasesOsmotic PressurePeptide HydrolasesPhosphatidylinositol 3-KinasesPhosphoproteinsProteasome Endopeptidase ComplexProtein KinasesProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptor, InsulinSignal TransductionTOR Serine-Threonine KinasesTumor Cells, CulturedUbiquitinConceptsInsulin-like growth factor-1Insulin/IGFMouse embryo fibroblastsProteasome-mediated degradationIRS-2Embryo fibroblastsInsulin/insulin-like growth factor-1 signalingInsulin receptor substrate (IRS) proteinsUbiquitin/proteasome-mediated degradationNovel negative feedback mechanismInsulin-like growth factor-1 signalingInsulin receptor substrate 2Inhibitor of phosphatidylinositolIRS-1 activationPeripheral insulin actionIGF-1 treatmentReceptor tyrosine kinasesHomologous receptor tyrosine kinasesGrowth factor-1IRS proteinsSubstrate proteinsBeta-cell survivalOsmotic stressTyrosine kinaseIRS-1
1999
Insulin action and type 2 diabetes: lessons from knockout mice
Withers D, White M. Insulin action and type 2 diabetes: lessons from knockout mice. Current Opinion In Endocrinology Diabetes And Obesity 1999, 6: 141-145. DOI: 10.1097/00060793-199904000-00010.Peer-Reviewed Original ResearchBeta-cell functionType 2 diabetesInsulin signal transduction pathwayInsulin receptor resultsSignal transduction pathwaysGlucose homeostasisInsulin receptor substrateClassical insulin target tissuesInsulin actionBeta cell-specific deletionCell functionPancreatic beta-cell functionPeripheral insulin actionKnockout mouse modelInsulin target tissuesCell-specific deletionTransduction pathwaysReceptor substrateSignaling pathwaysUnsuspected roleNew experimental modelInsulin resistanceNovel insightsNovel mechanismGlucose disposal