2008
Correction: A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice
Savage D, Zhai L, Ravikumar B, Choi C, Snaar J, McGuire A, Wou S, Medina-Gomez G, Kim S, Bock C, Segvich D, Solanky B, Deelchand D, Vidal-Puig A, Wareham N, Shulman G, Karpe F, Taylor R, Pederson B, Roach P, O'Rahilly S, DePaoli-Roach A. Correction: A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice. PLOS Medicine 2008, 5: e246. PMCID: PMC2605894, DOI: 10.1371/journal.pmed.0050246.Peer-Reviewed Original Research
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
2001
Regulation of Hepatic Glucose Uptake
Taylor R, Shulman G. Regulation of Hepatic Glucose Uptake. 2001, 787-802. DOI: 10.1002/cphy.cp070226.Peer-Reviewed Original ResearchHepatic glucose productionHepatic glucose uptakeGlucose productionGlucose uptakeHepatic glycogen storageLiver glycogen storesHepatic glycogen contentGlycogen storage diseaseNormal diurnal fluctuationsPortal signalPostprandial statePostabsorptive stateGlycogen storesGlycogen contentGlucagon regulationGlycogen storageHomeostatic mechanismsStorage diseaseGlycogen synthesisEarly adaptationMetabolismGlucose carbonCirrhosisStimulating Effects of Low-Dose Fructose on Insulin-Stimulated Hepatic Glycogen Synthesis in Humans
Petersen K, Laurent D, Yu C, Cline G, Shulman G. Stimulating Effects of Low-Dose Fructose on Insulin-Stimulated Hepatic Glycogen Synthesis in Humans. Diabetes 2001, 50: 1263-1268. PMID: 11375325, DOI: 10.2337/diabetes.50.6.1263.Peer-Reviewed Original ResearchConceptsNet hepatic glycogen synthesisHepatic glycogen synthesisGlycogen synthesisSynthase fluxInfusion of fructoseLow-dose infusionType 2 diabetesEuglycemic hyperinsulinemic conditionsPotential therapeutic valueHepatic glycogen metabolismThreefold increaseFructose studiesEuglycemic hyperinsulinemiaHyperinsulinemic conditionsFructose infusionControl studyTherapeutic valueInfusionType 1Glucokinase activityGlycogen metabolismIndirect pathwaysStimulating effectInsulinStimulationContribution of net hepatic glycogen synthesis to disposal of an oral glucose load in humans
Petersen K, Cline G, Gerard D, Magnusson I, Rothman D, Shulman G. Contribution of net hepatic glycogen synthesis to disposal of an oral glucose load in humans. Metabolism 2001, 50: 598-601. PMID: 11319724, DOI: 10.1053/meta.2001.22561.Peer-Reviewed Original ResearchConceptsHepatic glycogen synthesisOral glucose loadGlucose loadMagnetic resonance imagingLiver glycogen synthesisNet hepatic glycogen synthesisLiver volumeGlycogen synthesisWhole-body glucose disposalGlycogen contentHepatic glycogen concentrationIngestion of glucoseLiver glycogen contentHepatic glycogen contentIdentical glucose loadHepatic UDP-glucoseGlucose disposalGroup 2Group 1Direct pathwayResonance imagingGlycogen concentrationMean maximum rateLiverIngestion
2000
Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle
Kim J, Michael M, Previs S, Peroni O, Mauvais-Jarvis F, Neschen S, Kahn B, Kahn C, Shulman G. Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. Journal Of Clinical Investigation 2000, 105: 1791-1797. PMID: 10862794, PMCID: PMC378504, DOI: 10.1172/jci8305.Peer-Reviewed Original ResearchConceptsInsulin resistanceSelective insulin resistanceMIRKO miceType 2 diabetesHyperinsulinemic-euglycemic conditionsInsulin-stimulated muscle glucose transportMuscle glucose transportMuscle-specific inactivationPrediabetic syndromeGlucose transportControl miceFat massInsulin receptor geneInsulin actionMiceRedistribution of substratesSkeletal muscleImportant associationPotential mechanismsReceptor geneObesityGlycogen synthesisTissueMuscleAdiposityMechanism 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 infusionGlycogenGlycogen loading alters muscle glycogen resynthesis after exercise
Price T, Laurent D, Petersen K, Rothman D, Shulman G. Glycogen loading alters muscle glycogen resynthesis after exercise. Journal Of Applied Physiology 2000, 88: 698-704. PMID: 10658040, DOI: 10.1152/jappl.2000.88.2.698.Peer-Reviewed Original ResearchConceptsMaximum voluntary contractionGlycogen recoveryNOR trialMuscle glycogen resynthesisMuscle glycogen recoveryNormal resting levelsGlycogen resynthesisVoluntary contractionHeavy exercisePlantar flexionResting levelGlycogen concentrationGlycogen levelsSeparate occasionsSimilar glucoseUntrained subjectsTrialsGlycogen synthesisExerciseExtended recoverySubjectsRecoveryLevelsMinFlexion
1999
Metabolic control analysis of insulin-stimulated glucose disposal in rat skeletal muscle
Jucker B, Barucci N, Shulman G. Metabolic control analysis of insulin-stimulated glucose disposal in rat skeletal muscle. American Journal Of Physiology 1999, 277: e505-e512. PMID: 10484363, DOI: 10.1152/ajpendo.1999.277.3.e505.Peer-Reviewed Original ResearchConceptsInsulin-stimulated glucose disposalGlucose transport/phosphorylationGlucose disposalHyperinsulinemic clampAwake ratsInfusion protocolGlycogen synthesisSkeletal muscleGlucose infusion rateMuscle glucose disposalSkeletal muscle glucose disposalProtocol IRat skeletal muscleRate of glycolysisInfusion rateHindlimb musclesMajority of controlsImpaired 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 troglitazoneDiabetes
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 Research