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
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
1999
Insulin Receptor Substrate-2 Is Not Necessary for Insulin- and Exercise-stimulated Glucose Transport in Skeletal Muscle*
Higaki Y, Wojtaszewski J, Hirshman M, Withers D, Towery H, White M, Goodyear L. Insulin Receptor Substrate-2 Is Not Necessary for Insulin- and Exercise-stimulated Glucose Transport in Skeletal Muscle*. Journal Of Biological Chemistry 1999, 274: 20791-20795. PMID: 10409618, DOI: 10.1074/jbc.274.30.20791.Peer-Reviewed Original ResearchConceptsExercise-stimulated glucose transportInsulin-stimulated 2DG uptakeBlood glucose concentrationGlucose transportInsulin resistanceSkeletal muscleInsulin receptor substrate 2Glucose concentrationSkeletal muscle glucose transportHigher blood glucose concentrationsInsulin receptor substrate-2-deficient (IRS2(-/-)) miceOnset of diabetesType 2 diabetesWild-type miceMuscle glucose transportIRS2 proteinAbsence of insulinMuscle GLUT4 contentSubstrate 2WT animalsSoleus muscleGLUT4 contentLower basalMiceInsulin