2007
The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome
Petersen KF, Dufour S, Savage DB, Bilz S, Solomon G, Yonemitsu S, Cline GW, Befroy D, Zemany L, Kahn BB, Papademetris X, Rothman DL, Shulman GI. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 12587-12594. PMID: 17640906, PMCID: PMC1924794, DOI: 10.1073/pnas.0705408104.Peer-Reviewed Original ResearchConceptsPlasma high-density lipoprotein concentrationsHigh-density lipoprotein concentrationsHepatic de novo lipogenesisMuscle glycogen synthesisInsulin resistanceInsulin-resistant subjectsPlasma triglyceride concentrationsDe novo lipogenesisMetabolic syndromeAtherogenic dyslipidemiaIL-6Lipoprotein concentrationsTNF-alphaPlasma concentrationsTriglyceride concentrationsNovo lipogenesisGlycogen synthesisIntraabdominal fat volumeSkeletal muscle insulin resistanceSkeletal muscleProtein 4Skeletal muscle glycogen synthesisMuscle insulin resistanceHepatic triglyceride synthesisIntraabdominal obesity
2004
MRS Studies of the Role of the Muscle Glycogen Synthesis Pathway in the Pathophysiology of Type 2 Diabetes
Shulman G, Rothman D. MRS Studies of the Role of the Muscle Glycogen Synthesis Pathway in the Pathophysiology of Type 2 Diabetes. 2004, 45-57. DOI: 10.1002/0470011505.ch4.Peer-Reviewed Original Research
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
Impaired 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 conditionsPatientsCellular 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 troglitazoneDiabetesEffects 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
1998
Effect of epinephrine on muscle glycogenolysis and insulin-stimulated muscle glycogen synthesis in humans
Laurent D, Petersen K, Russell R, Cline G, Shulman G. Effect of epinephrine on muscle glycogenolysis and insulin-stimulated muscle glycogen synthesis in humans. American Journal Of Physiology 1998, 274: e130-e138. PMID: 9458758, DOI: 10.1152/ajpendo.1998.274.1.e130.Peer-Reviewed Original ResearchConceptsInsulin-stimulated muscle glycogen synthesisMuscle glycogen synthesisMuscle glycogenolysisEpinephrine infusionPhysiological increaseWhole-body glucose oxidationMuscle glycogen synthesis ratesPlasma epinephrine concentrationEuglycemic hyperinsulinemic clampGlucose infusion rateEffect of epinephrineGlycogen synthesisInsulin-stimulated glycogenesisBasal insulinControl subjectsPlasma glucoseEpinephrine concentrationsFree fatty acidsBasal valuesInfusion rateGlycogen synthesis rateMuscle glycogenEpinephrineGlycogenolysisMajor impairment
1997
Effects of insulin-like growth factor I on glucose metabolism in rats with liver cirrhosis
Petersen K, Jacob R, West A, Sherwin R, Shulman G. Effects of insulin-like growth factor I on glucose metabolism in rats with liver cirrhosis. American Journal Of Physiology 1997, 273: e1189-e1193. PMID: 9435535, DOI: 10.1152/ajpendo.1997.273.6.e1189.Peer-Reviewed Original ResearchConceptsMuscle glycogen synthesisInsulin-like growth factor ICirrhotic ratsGrowth factor IGlucose metabolismLiver cirrhosisGlycogen synthesisFactor IInsulin-stimulated muscle glycogen synthesisIGF-I therapyPeripheral glucose metabolismWhole-body glucose turnoverEndogenous glucose productionAbility of IGFEuglycemic clampInsulin resistanceControl ratsAwake ratsCirrhosisDiminished suppressionControl groupIGFRatsGlucose productionGlucose turnover
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 rateQuantification of Muscle Glycogen Synthesis in Normal Subjects and Subjects With Non-Insulin Dependent Diabetes by13 C Nuclear Magnetic Resonance Spectroscopy.
Shulman G, Rothman D, Jue T, Jette D. Quantification of Muscle Glycogen Synthesis in Normal Subjects and Subjects With Non-Insulin Dependent Diabetes by13 C Nuclear Magnetic Resonance Spectroscopy. Cardiopulmonary Physical Therapy Journal 1990, 1: 12-13. DOI: 10.1097/01823246-199001020-00010.Peer-Reviewed Original ResearchNon-Insulin DependentMuscle glycogen synthesisNormal subjectsGlycogen synthesisMagnetic resonance spectroscopySubjects