2024
Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity
Petersen M, Smith G, Palacios H, Farabi S, Yoshino M, Yoshino J, Cho K, Davila-Roman V, Shankaran M, Barve R, Yu J, Stern J, Patterson B, Hellerstein M, Shulman G, Patti G, Klein S. Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity. Cell Metabolism 2024, 36: 745-761.e5. PMID: 38569471, PMCID: PMC11025492, DOI: 10.1016/j.cmet.2024.03.002.Peer-Reviewed Original ResearchConceptsUnhealthy obesityPlasma PAI-1 concentrationAbnormalities associated with obesityMetabolically healthy obesityMetabolically unhealthy obesityPAI-1 concentrationsMetabolic heterogeneity of obesityHeterogeneity of obesityMetabolically healthy leanSystemic metabolic functionCharacteristics of peopleDecreased oxidative stressHealthy obesityCardiometabolic characteristicsAdipose tissue biologyHealthy leanSkeletal muscle biologyPlasma adiponectinPlasma glucoseObesityMetabolic heterogeneityOxidative stressPotential mechanismsTissue biologyMuscle biology
2020
Effect of a Low-Fat Vegan Diet on Body Weight, Insulin Sensitivity, Postprandial Metabolism, and Intramyocellular and Hepatocellular Lipid Levels in Overweight Adults
Kahleova H, Petersen KF, Shulman GI, Alwarith J, Rembert E, Tura A, Hill M, Holubkov R, Barnard ND. Effect of a Low-Fat Vegan Diet on Body Weight, Insulin Sensitivity, Postprandial Metabolism, and Intramyocellular and Hepatocellular Lipid Levels in Overweight Adults. JAMA Network Open 2020, 3: e2025454. PMID: 33252690, PMCID: PMC7705596, DOI: 10.1001/jamanetworkopen.2020.25454.Peer-Reviewed Original ResearchMeSH KeywordsAbsorptiometry, PhotonAdultAgedBlood GlucoseBody CompositionBody WeightCholesterolCholesterol, HDLCholesterol, LDLC-PeptideDiet, Fat-RestrictedDiet, VeganEnergy IntakeEnergy MetabolismFemaleGlycated HemoglobinHepatocytesHumansInsulinInsulin ResistanceIntra-Abdominal FatLipid MetabolismLiverMaleMiddle AgedMuscle Fibers, SkeletalMuscle, SkeletalObesityOverweightPostprandial PeriodProton Magnetic Resonance SpectroscopyTriglyceridesConceptsLow-fat vegan dietHomeostasis model assessment indexIntramyocellular lipid levelsModel assessment indexIntervention groupLipid levelsBody weightInsulin resistancePostprandial metabolismVegan dietOverweight adultsDietary interventionInsulin sensitivityThermic effectControl groupPlant-based dietary interventionDual X-ray absorptiometryInsulin resistance leadExcess body weightInsulin sensitivity indexType 2 diabetesMajor health problemProton magnetic resonance spectroscopyX-ray absorptiometrySubset of participantsDissociation of Muscle Insulin Resistance from Alterations in Mitochondrial Substrate Preference
Song JD, Alves TC, Befroy DE, Perry RJ, Mason GF, Zhang XM, Munk A, Zhang Y, Zhang D, Cline GW, Rothman DL, Petersen KF, Shulman GI. Dissociation of Muscle Insulin Resistance from Alterations in Mitochondrial Substrate Preference. Cell Metabolism 2020, 32: 726-735.e5. PMID: 33035493, PMCID: PMC8218871, DOI: 10.1016/j.cmet.2020.09.008.Peer-Reviewed Original Research
2003
Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance
Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI. Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance. Science 2003, 300: 1140-1142. PMID: 12750520, PMCID: PMC3004429, DOI: 10.1126/science.1082889.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAdolescentAdultAgedAged, 80 and overAgingBlood GlucoseBody Mass IndexFemaleHumansInsulinInsulin ResistanceLiverMaleMiddle AgedMitochondriaMitochondrial DiseasesMuscle, SkeletalNuclear Magnetic Resonance, BiomolecularOxidation-ReductionOxygen ConsumptionPhosphorylationTriglyceridesConceptsInsulin resistanceInsulin-stimulated muscle glucose metabolismType 2 diabetesMuscle glucose metabolismLean body massElderly study participantsAge-associated declineMitochondrial function contributesFat massFat accumulationGlucose metabolismYoung controlsStudy participantsLiver tissueFunction contributesMitochondrial dysfunctionYounger participantsPossible roleMitochondrial oxidativeBody massMagnetic resonance spectroscopyParticipantsDiabetesDysfunctionPathogenesis
2001
Effect 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 ResearchStimulating 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
Effects 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 musclesMechanism 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 recoverySubjectsRecoveryLevelsMinFlexionIntense exercise stimulates albumin synthesis in the upright posture
Nagashima K, Cline G, Mack G, Shulman G, Nadel E. Intense exercise stimulates albumin synthesis in the upright posture. Journal Of Applied Physiology 2000, 88: 41-46. PMID: 10642360, DOI: 10.1152/jappl.2000.88.1.41.Peer-Reviewed Original Research
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 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 cycleContributions 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 ResearchConceptsNet 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
Effect of insulin on glycerol production in obese adolescents
Robinson C, Tamborlane W, Maggs D, Enoksson S, Sherwin R, Silver D, Shulman G, Caprio S. Effect of insulin on glycerol production in obese adolescents. American Journal Of Physiology 1998, 274: e737-e743. PMID: 9575836, DOI: 10.1152/ajpendo.1998.274.4.e737.Peer-Reviewed Original ResearchConceptsNet lipid oxidationObese adolescentsLean adultsGlycerol turnoverTwo-step euglycemic-hyperinsulinemic clampFree fatty acid concentrationsBody fat massEuglycemic hyperinsulinemic clampSensitivity of adipocytesEffect of insulinAction of insulinObese groupLean subjectsInsulin resistanceAdipose massPlasma insulinFatty acid concentrationsAdolescent obesityFat massLean adolescentsImpaired stimulationPhysiological incrementsFFA levelsGlucose metabolismIndirect calorimetryEffect 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
Metabolic Defects in Lean Nondiabetic Offspring of NIDDM Parents: A Cross-Sectional Study
Perseghin G, Ghosh S, Gerow K, Shulman G. Metabolic Defects in Lean Nondiabetic Offspring of NIDDM Parents: A Cross-Sectional Study. Diabetes 1997, 46: 1001-1009. PMID: 9166672, DOI: 10.2337/diab.46.6.1001.Peer-Reviewed Original ResearchConceptsInsulin resistanceInsulin sensitivityControl subjectsInsulin secretionNIDDM parentsNIDDM patientsFFA metabolismFFA concentrationsAbove confounding factorsInsulin-resistant offspringFree fatty acid levelsInverse correlationLDL cholesterol levelsHealthy control subjectsNormal insulin sensitivityIntravenous glucose bolusLower insulin sensitivityPlasma FFA concentrationEuglycemic hyperinsulinemic clampCross-sectional studyFirst-degree relativesPathogenesis of NIDDMDefective insulin secretionFatty acid levelsHigh free fatty acid levels
1995
Contribution of Hepatic Glycogenolysis to Glucose Production in Humans in Response to a Physiological Increase in Plasma Glucagon Concentration
Magnusson I, Rothman D, Gerard D, Katz L, Shulman G. Contribution of Hepatic Glycogenolysis to Glucose Production in Humans in Response to a Physiological Increase in Plasma Glucagon Concentration. Diabetes 1995, 44: 185-189. PMID: 7859939, DOI: 10.2337/diab.44.2.185.Peer-Reviewed Original ResearchConceptsNet hepatic glycogenolysisLiver glycogen concentrationPlasma glucagon concentrationsHepatic glycogenolysisGlucagon concentrationsGlycogen concentrationLiver volumeGlucose productionPlasma glucose concentrationOverall glucose productionTwo-compartment modelHealthy subjectsPhysiological incrementsPhysiological increaseGlucose appearanceSame time periodMagnetic resonance imagesGlucose kineticsBaseline RaInfusionGlycogenolysisGlucose concentrationResonance imagesMumol