2014
Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease
Shulman GI. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. New England Journal Of Medicine 2014, 371: 1131-1141. PMID: 25229917, DOI: 10.1056/nejmra1011035.Peer-Reviewed Original Research
2013
Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy
Befroy DE, Perry RJ, Jain N, Dufour S, Cline GW, Trimmer JK, Brosnan J, Rothman DL, Petersen KF, Shulman GI. Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy. Nature Medicine 2013, 20: 98-102. PMID: 24317120, PMCID: PMC3947269, DOI: 10.1038/nm.3415.Peer-Reviewed Original Research
2004
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes. New England Journal Of Medicine 2004, 350: 664-671. PMID: 14960743, PMCID: PMC2995502, DOI: 10.1056/nejmoa031314.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdipose TissueBlood GlucoseDiabetes Mellitus, Type 2Fatty AcidsFemaleGlucoseGlucose Clamp TechniqueGlucose Tolerance TestGlycerolHumansInsulinInsulin ResistanceLipolysisMagnetic Resonance SpectroscopyMaleMitochondriaMuscle, SkeletalOxidative PhosphorylationTriglyceridesConceptsInsulin-resistant offspringType 2 diabetesIntramyocellular lipid contentInsulin-sensitive control subjectsMagnetic resonance spectroscopy studyInsulin resistanceControl subjectsProton magnetic resonance spectroscopy studyHyperinsulinemic-euglycemic clamp studiesTumor necrosis factor alphaImpaired mitochondrial activityIntrahepatic triglyceride contentDevelopment of diabetesChildren of patientsInsulin-resistant subjectsNecrosis factor alphaSensitivity of liverInsulin-stimulated ratesFatty acid metabolismMitochondrial oxidative phosphorylation activityInterleukin-6Intramyocellular lipidsPlasma concentrationsFactor alphaClamp studies
2001
NMR Spectroscopy in β Cell Engineering and Islet Transplantation
PAPAS K, COLTON C, GOUNARIDES J, ROOS E, JAREMA M, SHAPIRO M, CHENG L, CLINE G, SHULMAN G, WU H, BONNER‐WEIR S, WEIR G. NMR Spectroscopy in β Cell Engineering and Islet Transplantation. Annals Of The New York Academy Of Sciences 2001, 944: 96-119. PMID: 11797699, DOI: 10.1111/j.1749-6632.2001.tb03826.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineGenes, bcl-2Genes, mycGlucoseHumansIslets of LangerhansIslets of Langerhans TransplantationMagnetic Resonance SpectroscopyRatsTissue EngineeringConceptsIslet transplantationGlucose metabolismBeta cellsLong-term complicationsIrreversible damageTerm complicationsOxidative glucose metabolismAcute ischemiaTransplantationVivo efficacyHuman isletsIslet preparationsC-myc oncogeneSecreting tissueCell damageSuch exposureGenetic alterationsBcl-2Overnight incubationIslet transportationIsletsEffect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle
Lebon V, Dufour S, Petersen K, Ren J, Jucker B, Slezak L, Cline G, Rothman D, Shulman G. Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle. Journal Of Clinical Investigation 2001, 108: 733-737. PMID: 11544279, PMCID: PMC209375, DOI: 10.1172/jci11775.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdultCitric Acid CycleFemaleGlutamic AcidHumansMagnetic Resonance SpectroscopyMaleMitochondriaMuscle, SkeletalOxidative PhosphorylationTriiodothyronineConceptsSkeletal muscleContribution 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 ResearchMeSH KeywordsAdultBlood GlucoseCarbon IsotopesFastingFemaleGlucoseGlycogenHumansInsulinKineticsLiverMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMaleUridine Diphosphate GlucoseConceptsHepatic 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
13C/31P NMR Assessment of Mitochondrial Energy Coupling in Skeletal Muscle of Awake Fed and Fasted Rats RELATIONSHIP WITH UNCOUPLING PROTEIN 3 EXPRESSION*
Jucker B, Ren J, Dufour S, Cao X, Previs S, Cadman K, Shulman G. 13C/31P NMR Assessment of Mitochondrial Energy Coupling in Skeletal Muscle of Awake Fed and Fasted Rats RELATIONSHIP WITH UNCOUPLING PROTEIN 3 EXPRESSION*. Journal Of Biological Chemistry 2000, 275: 39279-39286. PMID: 10995775, DOI: 10.1074/jbc.m007760200.Peer-Reviewed Original ResearchAdenosine TriphosphateAlbuminsAnimalsBlotting, NorthernBlotting, WesternCarnitine O-PalmitoyltransferaseCarrier ProteinsEnzyme InhibitorsEpoxy CompoundsFatty AcidsFood DeprivationGlutamic AcidIon ChannelsKineticsMagnetic Resonance SpectroscopyMitochondriaMitochondrial ProteinsModels, BiologicalModels, ChemicalMuscle, SkeletalOxygenPalmitatesRatsRats, Sprague-DawleyRNA, MessengerTime FactorsTricarboxylic AcidsUncoupling Protein 3Effects of Caffeine on Muscle Glycogen Utilization and the Neuroendocrine Axis during Exercise1
Laurent D, Schneider K, Prusaczyk W, Franklin C, Vogel S, Krssak M, Petersen K, Goforth H, Shulman G. Effects of Caffeine on Muscle Glycogen Utilization and the Neuroendocrine Axis during Exercise1. The Journal Of Clinical Endocrinology & Metabolism 2000, 85: 2170-2175. PMID: 10852448, DOI: 10.1210/jcem.85.6.6655.Peer-Reviewed Original ResearchConceptsMuscle glycogen contentMuscle glycogen utilizationGlycogen contentCaffeine ingestionNeuroendocrine axisGlycogen utilizationGlycogen-sparing effectFree fatty acid concentrationsBeta-endorphin levelsCaffeine-treated groupExercise-induced glycogen depletionMaximal oxygen consumptionEffects of caffeineHigher muscle glycogen contentPlacebo groupExercise enduranceFatty acid concentrationsPlasma concentrationsNeuroendocrine hormonesCortisol releaseProlonged exerciseGlycogen depletionPlasma lactateNormal valuesThigh musclesAssessment of mitochondrial energy coupling in vivo by 13C/31P NMR
Jucker B, Dufour S, Ren J, Cao X, Previs S, Underhill B, Cadman K, Shulman G. Assessment of mitochondrial energy coupling in vivo by 13C/31P NMR. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 6880-6884. PMID: 10823916, PMCID: PMC18769, DOI: 10.1073/pnas.120131997.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCitric Acid CycleEnergy MetabolismMagnetic Resonance SpectroscopyMitochondriaObesityOxidation-ReductionRatsRats, Sprague-DawleyConceptsUCP3 mRNAMechanism 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 ResearchMeSH KeywordsAdultDietary CarbohydratesDose-Response Relationship, DrugExerciseFemaleGlucose-6-PhosphateGlycogenHumansMagnetic Resonance SpectroscopyMaleMuscle, SkeletalPhysical ExertionTime FactorsConceptsMaximum 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 ResearchMeSH KeywordsAnimalsBlood GlucoseFatty Acids, NonesterifiedGlucoseGlucose Clamp TechniqueGlucose-6-PhosphateGlycogenGlycolysisInsulinMagnetic Resonance SpectroscopyMuscle, SkeletalRatsRats, Sprague-DawleyConceptsInsulin-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 conditionsPatientsDetermination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR
Shen J, Petersen K, Behar K, Brown P, Nixon T, Mason G, Petroff O, Shulman G, Shulman R, Rothman D. Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8235-8240. PMID: 10393978, PMCID: PMC22218, DOI: 10.1073/pnas.96.14.8235.Peer-Reviewed Original ResearchConceptsGlutamate/glutamine cycleGlutamine cycleCerebral cortexMin/Rat cerebral cortexVivo 13C NMR spectraGlucose oxidation ratesHuman brainGlucose oxidationGlutamatergic activityRat modelTricarboxylic acid cycle rateParietal lobeHuman cortexCortexTime courseBrainGlutamine synthesisMajor metabolic fluxCycle rateTricarboxylic acid cycleHigh levelsInfusionRatsAcid cycleCellular 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 ResearchMeSH KeywordsDiabetes Mellitus, Type 2GlucoseGlycogenHumansHypoglycemic AgentsInsulinInsulin ResistanceLiverMagnetic Resonance SpectroscopyMusclesConceptsType 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 troglitazoneDiabetesContributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis
Petersen K, Krssak M, Navarro V, Chandramouli V, Hundal R, Schumann W, Landau B, Shulman G. Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis. American Journal Of Physiology 1999, 276: e529-e535. PMID: 10070020, DOI: 10.1152/ajpendo.1999.276.3.e529.Peer-Reviewed Original ResearchMeSH KeywordsAdultDeuterium OxideFastingFemaleGluconeogenesisGlucoseGlycogenHumansLiverLiver CirrhosisMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMaleReference ValuesConceptsNet hepatic glycogenolysisCirrhotic subjectsHepatic glycogenolysisControl subjectsGlucose productionFree insulin-like growth factor IInsulin-like growth factor IHepatic glycogen concentrationGrowth factor IHepatic glycogen contentMagnetic resonance imagingRate of gluconeogenesisBlood glucosePlasma levelsHealthy subjectsEffects 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 PIIntramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study
Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Shulman G, Roden M. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 1999, 42: 113-116. PMID: 10027589, DOI: 10.1007/s001250051123.Peer-Reviewed Original ResearchConceptsIntramyocellular lipid concentrationsIntramyocellular lipid contentInsulin sensitivityLipid concentrationsPlasma non-esterified fatty acid concentrationsNon-esterified fatty acid concentrationsWhole-body insulin sensitivityNon-diabetic adultsNon-esterified fatty acidsBody insulin sensitivityNon-obese humansMuscle biopsy studiesCross-sectional analysisInsulin resistanceIntramuscular lipid contentBiopsy studiesClamp testFatty acid concentrationsLipid contentPlasma concentrationsSoleus muscleLinear regression analysisPmol/Inverse correlationM values
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 ResearchMeSH KeywordsAnimalsBlood GlucoseCarbon IsotopesGlucoseGlycogenHyperglycemiaInsulinIntracellular FluidMagnetic Resonance SpectroscopyMaleMannitolMusclesRatsRats, Sprague-DawleyEffect 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