2005
Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents
Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. Journal Of Clinical Investigation 2005, 115: 3587-3593. PMID: 16284649, PMCID: PMC1280967, DOI: 10.1172/jci25151.Peer-Reviewed Original ResearchMeSH KeywordsBiopsyBlood GlucoseBlotting, WesternBody Mass IndexBody WeightDiabetes Mellitus, Type 2DNA, MitochondrialFamily HealthFemaleGene Expression RegulationGlucose Clamp TechniqueGlucose Tolerance TestHumansHyperinsulinismImmunoprecipitationInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceLipidsMaleMicroscopy, ElectronMicroscopy, Electron, TransmissionMitochondriaMusclesPhosphoproteinsPhosphorylationProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSerineSignal TransductionTime FactorsTranscription, GeneticTriglyceridesConceptsInsulin-resistant offspringIR offspringType 2 diabetesInsulin-stimulated muscle glucose uptakeType 2 diabetic parentsIntramyocellular lipid contentHyperinsulinemic-euglycemic clampMuscle glucose uptakeIRS-1 serine phosphorylationMuscle mitochondrial densityMitochondrial densityMuscle biopsy samplesSerine kinase cascadeInsulin-stimulated Akt activationDiabetic parentsInsulin resistanceControl subjectsBiopsy samplesGlucose uptakeLipid accumulationMitochondrial dysfunctionInsulin signalingAkt activationEarly defectsMuscle
2001
Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance
Zabolotny J, Kim Y, Peroni O, Kim J, Pani M, Boss O, Klaman L, Kamatkar S, Shulman G, Kahn B, Neel B. Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 5187-5192. PMID: 11309481, PMCID: PMC33185, DOI: 10.1073/pnas.071050398.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood GlucoseBody CompositionCreatine KinaseCreatine Kinase, MM FormFatty Acids, NonesterifiedHumansInsulinInsulin ResistanceIntracellular Signaling Peptides and ProteinsIsoenzymesMiceMice, TransgenicMusclesOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphorylationPhosphotyrosinePromoter Regions, GeneticProtein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesRecombinant Fusion ProteinsSignal TransductionConceptsIRS proteinsLAR protein tyrosine phosphataseKinase activityProtein tyrosine phosphatase LARIRS-2Insulin receptor substrate-1Protein tyrosine phosphatasePI3-kinase activityInsulin-resistant humansReceptor substrate-1Association of p85alphaInsulin resistanceInsulin-responsive tissuesHuman LARTyrosyl phosphorylationInsulin target tissuesTransgenic miceSubstrate-1IRS-1Wild-type controlsInsulin receptorWhole-body glucose disposalWhole-body insulin resistancePhosphotyrosinePhosphorylation
2000
Contrasting Effects of IRS-1 Versus IRS-2 Gene Disruption on Carbohydrate and Lipid Metabolism in Vivo *
Previs S, Withers D, Ren J, White M, Shulman G. Contrasting Effects of IRS-1 Versus IRS-2 Gene Disruption on Carbohydrate and Lipid Metabolism in Vivo *. Journal Of Biological Chemistry 2000, 275: 38990-38994. PMID: 10995761, DOI: 10.1074/jbc.m006490200.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsCarbohydrate MetabolismFatty Acids, NonesterifiedFood DeprivationGas Chromatography-Mass SpectrometryGlucoseGlycerolInsulinInsulin Receptor Substrate ProteinsIntracellular Signaling Peptides and ProteinsLipid MetabolismLiverMaleMiceMusclesMutationPhenotypePhosphoproteinsRadioimmunoassayTime FactorsConceptsLipid metabolismInsulin resistanceIRS-2Glucose utilizationPlasma free fatty acid concentrationsWhole-body glucose utilizationGlycerol turnoverFree fatty acid concentrationsMarked insulin resistancePeripheral glucose metabolismPeripheral glucose utilizationHyperinsulinemic-euglycemic clampEndogenous glucose productionIRS-1Effect of insulinHepatic glycogen synthesisWT miceFatty acid concentrationsInsulin receptor substrateGlucose metabolismFasted miceAdipose tissueReduced suppressionGlucose productionMiceMechanism of Insulin Resistance in A-ZIP/F-1 Fatless Mice*
Kim J, Gavrilova O, Chen Y, Reitman M, Shulman G. Mechanism of Insulin Resistance in A-ZIP/F-1 Fatless Mice*. Journal Of Biological Chemistry 2000, 275: 8456-8460. PMID: 10722680, DOI: 10.1074/jbc.275.12.8456.Peer-Reviewed Original ResearchConceptsType 2 diabetesInsulin resistanceFatless miceInsulin actionTriglyceride contentA-ZIP/FDevelopment of diabetesLiver triglyceride contentHyperinsulinemic-euglycemic clampAccumulation of triglyceridesMuscle/liverWild-type littermatesInsulin receptor substrate-1Receptor substrate-1Partitioning of fatSubsequent impairmentDiabetesFat metabolismMiceFat tissueLiverInsulin signalingMuscleLatter tissueSubstrate-1
1999
Cellular mechanisms of insulin resistance in humans
Shulman G. Cellular mechanisms of insulin resistance in humans. The American Journal Of Cardiology 1999, 84: 3-10. PMID: 10418851, DOI: 10.1016/s0002-9149(99)00350-1.Peer-Reviewed Original ResearchConceptsType 2 diabetesInsulin resistanceMuscle glycogen synthesisFree fatty acidsGlucose productionHepatic gluconeogenesisInsulin-stimulated glucose metabolismInsulin-stimulated muscle glycogen synthesisBetter glucose controlCellular mechanismsHepatic glucose productionLiver glycogen concentrationGlycogen synthesisPathophysiologic defectsCombination therapyGlucose controlInsulin secretionInsulin receptor substrateHyperinsulinemic clampingPeripheral tissuesGlucose clearanceFFA levelsGlucose metabolismThiazolidinedione troglitazoneDiabetes
1998
A novel 13C NMR method to assess intracellular glucose concentration in muscle, in vivo
Cline G, Jucker B, Trajanoski Z, Rennings A, Shulman G. A novel 13C NMR method to assess intracellular glucose concentration in muscle, in vivo. American Journal Of Physiology 1998, 274: e381-e389. PMID: 9486172, DOI: 10.1152/ajpendo.1998.274.2.e381.Peer-Reviewed Original Research
1992
Validation of 13c nmr measurement of human skeletal muscle glycogen by direct biochemical assay of needle biopsy samples
Taylor R, Price T, Rothman D, Shulman R, Shulman G. Validation of 13c nmr measurement of human skeletal muscle glycogen by direct biochemical assay of needle biopsy samples. Magnetic Resonance In Medicine 1992, 27: 13-20. PMID: 1435198, DOI: 10.1002/mrm.1910270103.Peer-Reviewed Original Research
1991
N.m.r. studies of muscle glycogen synthesis in normal and non-insulin-dependent diabetic subjects
Rothman D, Shulman R, Shulman G. N.m.r. studies of muscle glycogen synthesis in normal and non-insulin-dependent diabetic subjects. Biochemical Society Transactions 1991, 19: 992-994. PMID: 1794599, DOI: 10.1042/bst0190992.Peer-Reviewed Original Research
1990
Effect of metformin treatment on insulin action in diabetic rats: In vivo and in vitro correlations
Rossetti L, DeFronzo R, Gherzi R, Stein P, Andraghetti G, Falzetti G, Shulman G, Klein-Robbenhaar E, Cordera R. Effect of metformin treatment on insulin action in diabetic rats: In vivo and in vitro correlations. Metabolism 1990, 39: 425-435. PMID: 2157941, DOI: 10.1016/0026-0495(90)90259-f.Peer-Reviewed Original ResearchConceptsInsulin receptor tyrosine kinase activityDiabetic ratsMetformin treatmentReceptor tyrosine kinase activityTyrosine kinase activitySupernormal levelsGlucose disposalInsulin-mediated whole-body glucose disposalTotal body insulin-mediated glucose disposalInsulin actionNeonatal streptozotocin diabetic ratsTotal body glucose uptakeInsulin-mediated glucose disposalWhole-body glucose disposalGlucose uptakeDeficient insulin responseNormalized glucose toleranceInsulin clamp studiesStreptozotocin-diabetic ratsVivo insulin actionHepatic glucose productionMuscle glycogen synthesisGlycogen synthesisSynthetic rateGlucose toleranceQuantitation of Muscle Glycogen Synthesis in Normal Subjects and Subjects with Non-Insulin-Dependent Diabetes by 13C Nuclear Magnetic Resonance Spectroscopy
Shulman G, Rothman D, Jue T, Stein P, DeFronzo R, Shulman R. Quantitation of Muscle Glycogen Synthesis in Normal Subjects and Subjects with Non-Insulin-Dependent Diabetes by 13C Nuclear Magnetic Resonance Spectroscopy. New England Journal Of Medicine 1990, 322: 223-228. PMID: 2403659, DOI: 10.1056/nejm199001253220403.Peer-Reviewed Original ResearchConceptsMuscle glycogen synthesisNonoxidative glucose metabolismDiabetic subjectsNormal subjectsGlucose metabolismMuscle glycogenGlycogen synthesisHyperglycemic-hyperinsulinemic clamp studiesTotal body glucose uptakeWeight-matched healthy subjectsNon-insulin dependent diabetesSteady-state plasma concentrationsGlucose uptakeMean glucose uptakeDependent diabetes mellitusDiabetes mellitusInsulin resistanceGlucose disposalPlasma concentrationsHealthy subjectsStudy groupClamp studiesGastrocnemius muscleInsulin actionMean rate