2001
Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance
Yang C, Coker K, Kim J, Mora S, Thurmond D, Davis A, Yang B, Williamson R, Shulman G, Pessin J. Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance. Journal Of Clinical Investigation 2001, 107: 1311-1318. PMID: 11375421, PMCID: PMC209300, DOI: 10.1172/jci12274.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipose Tissue, BrownAnimalsBiological TransportGlucoseGlucose Clamp TechniqueGlucose Tolerance TestGlucose Transporter Type 4GlycogenGlycolysisHeterozygoteInsulin ResistanceLiverMembrane ProteinsMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsMuscle, SkeletalQa-SNARE ProteinsConceptsHeterozygous knockout miceInsulin-stimulated glucose uptakeGlucose uptakeKnockout miceNormal insulin-stimulated glucose uptakeWhole-body glucose uptakeHyperinsulinemic-euglycemic clamp procedureInsulin-stimulated glucose metabolismInsulin-stimulated GLUT4 translocationSkeletal muscleGLUT4 vesicle traffickingImpaired glucose toleranceMuscle insulin resistanceEarly embryonic lethalitySkeletal muscle glucose transportMuscle glucose transportCritical physiological roleGlucose toleranceInsulin resistanceClamp procedureVesicle traffickingSyntaxin 4Embryonic lethalityGlucose metabolismAnimal modelsAdipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver
Abel E, Peroni O, Kim J, Kim Y, Boss O, Hadro E, Minnemann T, Shulman G, Kahn B. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001, 409: 729-733. PMID: 11217863, DOI: 10.1038/35055575.Peer-Reviewed Original ResearchConceptsInsulin-stimulated glucose uptakeType 2 diabetesInsulin resistanceGlucose uptakeAdipose tissueGLUT4 expressionInsulin-resistant statesDownregulation of GLUT4Glucose intoleranceGlucose transportAdipose massIntracellular storage sitesGlucose homeostasisInsulin actionDiabetesPhosphoinositide-3-OH kinaseImpaired activationSkeletal muscleMuscleMicePlasma membrane4Early defectsLiverMain siteAdipocytes
1999
Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR
Russell R, Bergeron R, Shulman G, Young L. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. American Journal Of Physiology 1999, 277: h643-h649. PMID: 10444490, DOI: 10.1152/ajpheart.1999.277.2.h643.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsBiological TransportEnzyme ActivationGlucoseGlucose Transporter Type 4In Vitro TechniquesMaleMonosaccharide Transport ProteinsMultienzyme ComplexesMuscle ProteinsMyocardiumProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyRibonucleotidesSarcolemmaConceptsAMPK activationGLUT-4 translocationGLUT-4Glucose uptakeProtein kinase activityActivator of AMPKActivation of AMPKInsulin-stimulated increasePI3K-independent pathwayInsulin-stimulated glucose uptakePI3K inhibitorsKinase activityAICARDeoxyglucose uptakeAMPKTranslocationIschemia-induced translocationK inhibitorsAdenine 9Myocyte sarcolemmaPathwayImmunofluorescence studiesMuscle glucose uptakeActivationCardiac myocytesImpaired Glucose Transport as a Cause of Decreased Insulin-Stimulated Muscle Glycogen Synthesis in Type 2 Diabetes
Cline G, Petersen K, Krssak M, Shen J, Hundal R, Trajanoski Z, Inzucchi S, Dresner A, Rothman D, Shulman G. Impaired Glucose Transport as a Cause of Decreased Insulin-Stimulated Muscle Glycogen Synthesis in Type 2 Diabetes. New England Journal Of Medicine 1999, 341: 240-246. PMID: 10413736, DOI: 10.1056/nejm199907223410404.Peer-Reviewed Original ResearchConceptsMuscle glycogen synthesisType 2 diabetes mellitusConcentrations of insulinNormal subjectsDiabetes mellitusGlucose metabolismGlycogen synthesisGlucose concentrationWhole-body glucose metabolismInsulin-stimulated muscle glycogen synthesisIntracellular glucose concentrationType 2 diabetesPlasma insulin concentrationGlucose transportImpaired glucose transportInterstitial fluid glucose concentrationsOpen-flow microperfusionIntramuscular glucoseInterstitial fluidGlucose-6-phosphate concentrationInsulin resistanceVivo microdialysisInsulin concentrationsHyperinsulinemic conditionsPatientsRegulation of myocardial glucose uptake and transport during ischemia and energetic stress
Young L, Russell R, Yin R, Caplan M, Ren J, Bergeron R, Shulman G, Sinusas A. Regulation of myocardial glucose uptake and transport during ischemia and energetic stress. The American Journal Of Cardiology 1999, 83: 25-30. PMID: 10750583, DOI: 10.1016/s0002-9149(99)00253-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEnergetic stressEnergy-generating metabolic pathwaysMonophosphate-activated protein kinaseGlucose uptakeGlucose transport proteinProtein kinaseTransporter translocationTransport proteinsMolecular mechanismsMetabolic pathwaysCardiac glucose uptakeGlucose transporterCellular mechanismsGlucose transportFuel gaugeKinaseTranslocationGlucose entryModerate regional ischemiaSubsequent metabolismGlucose utilization increasesImportant roleUptakeGLUT4StressEffect of AMPK activation on muscle glucose metabolism in conscious rats
Bergeron R, Russell R, Young L, Ren J, Marcucci M, Lee A, Shulman G. Effect of AMPK activation on muscle glucose metabolism in conscious rats. American Journal Of Physiology 1999, 276: e938-e944. PMID: 10329989, DOI: 10.1152/ajpendo.1999.276.5.e938.Peer-Reviewed Original ResearchMeSH KeywordsAminoimidazole CarboxamideAMP-Activated Protein KinasesAndrostadienesAnimalsBiological TransportDeoxyglucoseElectric StimulationEnzyme ActivationEnzyme InhibitorsIn Vitro TechniquesInsulinMaleMultienzyme ComplexesMuscle ContractionMuscle, SkeletalPhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyRibonucleotidesTritiumWortmanninConceptsMuscle glucose metabolismGlucose transport activityActivation of AMPKGlucose uptakeGlucose metabolismTransport activitySkeletal muscle glucose metabolismExercise-induced increaseSkeletal muscle glucose transport activityBasal rateAbsence of wortmanninAdenosine receptor antagonistAdditive effectProtein kinase activationVariable infusionConscious ratsReceptor antagonistSaline infusionAwake ratsMedial gastrocnemiusElectrical stimulationEpitrochlearis musclesCellular pathwaysAMPK activationKinase activation
1998
Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo
Russell R, Yin R, Caplan M, Hu X, Ren J, Shulman G, Sinusas A, Young L. Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo. Circulation 1998, 98: 2180-2186. PMID: 9815873, DOI: 10.1161/01.cir.98.20.2180.Peer-Reviewed Original Research
1997
Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo.
Young L, Renfu Y, Russell R, Hu X, Caplan M, Ren J, Shulman G, Sinusas A. Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo. Circulation 1997, 95: 415-22. PMID: 9008459, DOI: 10.1161/01.cir.95.2.415.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological TransportDogsFluorescent Antibody TechniqueGlucose Transporter Type 1Glucose Transporter Type 4HeartIntracellular MembranesMonosaccharide Transport ProteinsMuscle ProteinsMyocardial IschemiaMyocardiumRegional Blood FlowSarcolemmaSubcellular FractionsTissue Distribution