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
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 3Contrasting 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 productionMicePersistent Changes in Myocardial Glucose Metabolism In Vivo During Reperfusion of a Limited-Duration Coronary Occlusion
McNulty P, Jagasia D, Cline G, Ng C, Whiting J, Garg P, Shulman G, Soufer R. Persistent Changes in Myocardial Glucose Metabolism In Vivo During Reperfusion of a Limited-Duration Coronary Occlusion. Circulation 2000, 101: 917-922. PMID: 10694532, DOI: 10.1161/01.cir.101.8.917.Peer-Reviewed Original ResearchConceptsCoronary occlusionGlucose metabolismPostischemic stunningAnterolateral left ventricleHeart glucose metabolismCoronary artery occlusionRegional glucose metabolismMyocardial glucose metabolismRegional myocardial ischemiaRegional mechanical functionRapid reperfusionReversible coronary occlusionArtery occlusionMyocardial ischemiaIntact ratsPreferential shuntingBlood flowReperfusionTracer uptakeLeft ventricleGlycogen depletionMetabolic signaturesOcclusionPersistent changesSustained changesGlycogen 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
Determination 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 cycle
1996
Time course of the defective α-cell response to hypoglycemia in diabetic BB rats
Jacob R, Dziura J, Morgen J, Shulman G, Sherwin R. Time course of the defective α-cell response to hypoglycemia in diabetic BB rats. Metabolism 1996, 45: 1422-1426. PMID: 8931649, DOI: 10.1016/s0026-0495(96)90125-0.Peer-Reviewed Original ResearchConceptsInsulin-dependent diabetes mellitusDays of diabetesBB ratsBB/Wor ratsNondiabetic BB ratsΑ-cell responseDiabetic BB ratsCourse of diabetesPancreatic glucagon levelsPancreatic glucagon contentBeta-cell functionPancreatic insulin contentHypoglycemic challengeCounterregulatory responsesDiabetes onsetDiabetes mellitusGlucagon levelsGlucagon releasePlasma glucagonGlucagon concentrationsInsulin clampGlucagon contentBaseline plasmaDisease onsetGroup 2
1994
Localized 13C NMR Spectroscopy in the Human Brain of Amino Acid Labeling from d‐[1‐13C]Glucose
Gruetter R, Novotny E, Boulware S, Mason G, Rothman D, Shulman G, Prichard J, Shulman R. Localized 13C NMR Spectroscopy in the Human Brain of Amino Acid Labeling from d‐[1‐13C]Glucose. Journal Of Neurochemistry 1994, 63: 1377-1385. PMID: 7931289, DOI: 10.1046/j.1471-4159.1994.63041377.x.Peer-Reviewed Original Research
1985
Metabolic Response to Three Years of Continuous, Basal Rate Intravenous Insulin Infusion in Type II Diabetic Patients*
BLACKSHEAR P, SHULMAN G, ROUSSELL A, NATHAN D, MINAKER K, ROWE J, ROBBINS D, COHEN A. Metabolic Response to Three Years of Continuous, Basal Rate Intravenous Insulin Infusion in Type II Diabetic Patients*. The Journal Of Clinical Endocrinology & Metabolism 1985, 61: 753-760. PMID: 3897260, DOI: 10.1210/jcem-61-4-753.Peer-Reviewed Original ResearchConceptsType II diabetic patientsII diabetic patientsInsulin clamp studiesDiabetic patientsInsulin infusionClamp studiesObese type II diabetic patientsEuglycemic insulin clamp studiesInfusion pumpVitreous fluorescein concentrationHemoglobin A1c levelsMonths of treatmentGlucose disposal rateIntravenous insulin infusionNormal glycemic controlSerum triglyceride concentrationBlood glucose levelsInfusion of insulinImplantable infusion pumpInsulin infusion pumpA1c levelsGlycemic controlSignificant hypoglycemiaImmunoreactive insulinPlasma glucose