2014
Muscle-specific activation of Ca2+/calmodulin-dependent protein kinase IV increases whole-body insulin action in mice
Lee HY, Gattu AK, Camporez JP, Kanda S, Guigni B, Kahn M, Zhang D, Galbo T, Birkenfeld AL, Jornayvaz FR, Jurczak MJ, Choi CS, Yan Z, Williams RS, Shulman GI, Samuel VT. Muscle-specific activation of Ca2+/calmodulin-dependent protein kinase IV increases whole-body insulin action in mice. Diabetologia 2014, 57: 1232-1241. PMID: 24718953, PMCID: PMC5634138, DOI: 10.1007/s00125-014-3212-1.Peer-Reviewed Original ResearchConceptsMitochondrial contentDependent protein kinaseDependent protein kinase IVSkeletal muscleInsulin actionMuscle mitochondrial contentInsulin-stimulated glucose uptakeMuscle-specific activationΓ coactivator 1αGlucose uptakePhosphorylation of AktSkeletal muscle insulin actionProtein kinaseOxidative type IMitochondrial biogenesisKinase IVMuscle insulin actionGLUT4 proteinGlucose metabolismInsulin-stimulated whole-body glucose uptakePleiotropic effectsWhole-body glucose uptakeCAMK4Coactivator 1αWhole-body insulin action
2010
Knockdown of the gene encoding Drosophila tribbles homologue 3 (Trib3) improves insulin sensitivity through peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in a rat model of insulin resistance
Weismann D, Erion DM, Ignatova-Todorava I, Nagai Y, Stark R, Hsiao JJ, Flannery C, Birkenfeld AL, May T, Kahn M, Zhang D, Yu XX, Murray SF, Bhanot S, Monia BP, Cline GW, Shulman GI, Samuel VT. Knockdown of the gene encoding Drosophila tribbles homologue 3 (Trib3) improves insulin sensitivity through peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in a rat model of insulin resistance. Diabetologia 2010, 54: 935-944. PMID: 21190014, PMCID: PMC4061906, DOI: 10.1007/s00125-010-1984-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzhydryl CompoundsDiabetes Mellitus, Type 2Disease Models, AnimalEpoxy CompoundsGlucose Clamp TechniqueImmunoblottingInsulin ResistanceMaleOligonucleotides, AntisensePPAR gammaProtein KinasesProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionConceptsTribbles homologue 3Euglycaemic hyperinsulinaemic clampWhite adipose tissueInsulin sensitivityAdipose tissueAntisense oligonucleotideInsulin-stimulated whole-body glucose uptakeWhole-body glucose uptakeConclusions/interpretationThese dataTissue-specific insulin sensitivityGlucose uptakeSkeletal muscle glucose uptakeWhite adipose tissue massPlasma HDL cholesterolRole of PPARAdipose tissue massMuscle glucose uptakeEndogenous glucose productionExpression of PPARInsulin-sensitising effectsDependent mannerViral proto-oncogeneHDL cholesterolAkt2 activityInsulin resistance
2001
Prevention of fat-induced insulin resistance by salicylate
Kim J, Kim Y, Fillmore J, Chen Y, Moore I, Lee J, Yuan M, Li Z, Karin M, Perret P, Shoelson S, Shulman G. Prevention of fat-induced insulin resistance by salicylate. Journal Of Clinical Investigation 2001, 108: 437-446. PMID: 11489937, PMCID: PMC209353, DOI: 10.1172/jci11559.Peer-Reviewed Original ResearchConceptsType 2 diabetesLipid infusionInsulin resistanceGlucose uptakeInsulin actionWhole-body glucose uptakeFat-induced insulin resistanceSkeletal muscleHigh-dose salicylatesHyperinsulinemic-euglycemic clampWild-type miceInsulin-stimulated glucose uptakeSkeletal muscle insulinIRS-1-associated PISerine kinase cascadeLipid-induced effectsAwake ratsAwake miceKnockout miceMuscle insulinInfusionTherapeutic agentsSalicylate actionKinase cascadeIKK betaGlucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4
Kim J, Zisman A, Fillmore J, Peroni O, Kotani K, Perret P, Zong H, Dong J, Kahn C, Kahn B, Shulman G. Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4. Journal Of Clinical Investigation 2001, 108: 153-160. PMID: 11435467, PMCID: PMC353719, DOI: 10.1172/jci10294.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAge of OnsetAnimalsDepression, ChemicalDiabetes Mellitus, Type 2Disease Models, AnimalGlucoseGlucose Transporter Type 4HyperglycemiaInsulinInsulin Infusion SystemsInsulin ResistanceKidney TubulesLiverMaleMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsMuscle, SkeletalPhlorhizinPrediabetic StateProtein TransportConceptsDevelopment of diabetesMuscle glucose uptakeKO miceHepatic glucose productionInsulin-stimulated glucose uptakeGlucose toxicityMuscle-specific inactivationGlucose uptakeAdipose tissueInsulin-stimulated muscle glucose uptakeGlucose productionWhole-body glucose uptakeSkeletal muscle glucose uptakeAdipose tissue glucose uptakeSuppress hepatic glucose productionTissue glucose uptakeHyperinsulinemic-euglycemic clampMuscle glucose transportInsulin resistanceTransgenic miceDiabetes phenotypeInsulin actionPhloridzin treatmentInsulin's abilityDiabetesSyntaxin 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 models
2000
Mechanism of muscle glycogen autoregulation in humans
Laurent D, Hundal R, Dresner A, Price T, Vogel S, Petersen K, Shulman G. Mechanism of muscle glycogen autoregulation in humans. AJP Endocrinology And Metabolism 2000, 278: e663-e668. PMID: 10751200, DOI: 10.1152/ajpendo.2000.278.4.e663.Peer-Reviewed Original ResearchConceptsInsulin-stimulated ratesWhole body glucose oxidation ratesMuscle glycogenGlycogen loadingPlasma free fatty acid concentrationsWhole-body glucose uptakeFree fatty acid concentrationsMuscle glycogen contentGlucose oxidation ratesMuscle glycogen synthesisPlasma lactate concentrationTwofold increaseHyperinsulinemic clampGlycogen synthase activityFatty acid concentrationsLoading protocolGlucose infusionHealthy volunteersLactate concentrationGlycogen contentGlucose uptakeAnaerobic glycolysisGlycogen synthesisUnlabeled glucose infusionGlycogen
1999
Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity
Dresner A, Laurent D, Marcucci M, Griffin M, Dufour S, Cline G, Slezak L, Andersen D, Hundal R, Rothman D, Petersen K, Shulman G. Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity. Journal Of Clinical Investigation 1999, 103: 253-259. PMID: 9916137, PMCID: PMC407880, DOI: 10.1172/jci5001.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultFatty Acids, NonesterifiedFemaleGlucoseGlucose Clamp TechniqueGlucose-6-PhosphateGlycerolGlycogenHumansHyperinsulinismInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLipid MetabolismMagnetic Resonance SpectroscopyMaleMuscle, SkeletalPhosphatidylinositol 3-KinasesPhosphoproteinsConceptsFree fatty acidsIRS-1-associated phosphatidylinositolLipid infusionInsulin resistanceGlycerol infusionPlasma free fatty acidsWhole-body glucose uptakeFive-hour infusionLipid/heparinHyperinsulinemic-euglycemic clampGlucose concentrationGlucose transportMuscle glycogen synthesisDiminished glucose transportMuscle biopsy samplesHuman skeletal muscleRate of insulinGlucose-6-phosphate concentrationFatty acidsHealthy subjectsBiopsy samplesInfusion studiesIdentical protocolInfusionIRS-1-associated PI
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