2024
Effect of Weight Loss on Skeletal Muscle Bioactive Lipids in People with Obesity and Type 2 Diabetes.
Petersen M, Yoshino M, Smith G, Gaspar R, Kahn M, Samovski D, Shulman G, Klein S. Effect of Weight Loss on Skeletal Muscle Bioactive Lipids in People with Obesity and Type 2 Diabetes. Diabetes 2024 PMID: 39264820, DOI: 10.2337/db24-0083.Peer-Reviewed Original ResearchMuscle insulin sensitivitySkeletal muscle insulin sensitivityType 2 diabetesEffects of weight lossInsulin sensitivityWeight lossWeight loss-induced improvementWhole-body insulin sensitivityObesityGlucose tracer infusionAssociated with changesHyperinsulinemic-euglycemic clamp procedureCeramide contentSn-1,2-DAGMuscle
2016
Mitochondrial Protonophores For Treatment of NAFLD/NASH and Type 2 Diabetes
Shulman G. Mitochondrial Protonophores For Treatment of NAFLD/NASH and Type 2 Diabetes. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.257.2.Peer-Reviewed Original ResearchType 2 diabetesInsulin resistanceLipid-induced insulin resistanceNAFLD/NASHSkeletal muscleAdipose tissue inflammationEctopic lipid depositionNon-alcoholic steatohepatitisAmerican Diabetes AssociationEctopic lipid depositsAlcoholic steatohepatitisDiabetes AssociationTissue inflammationRecent studiesLipid depositionType 2Lipid depositsHepatic gluconeogenesisCellular mechanismsMitochondrial protonophoreDiabetesMitochondrial inefficiencyLiverMuscleMolecular triggers
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
2001
Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver
Abel E, Peroni O, Kim J, Kim Y, Boss O, Hadro E, Minnemann T, Shulman G, Kahn B. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001, 409: 729-733. PMID: 11217863, DOI: 10.1038/35055575.Peer-Reviewed Original ResearchConceptsInsulin-stimulated glucose uptakeType 2 diabetesInsulin resistanceGlucose uptakeAdipose tissueGLUT4 expressionInsulin-resistant statesDownregulation of GLUT4Glucose intoleranceGlucose transportAdipose massIntracellular storage sitesGlucose homeostasisInsulin actionDiabetesPhosphoinositide-3-OH kinaseImpaired activationSkeletal muscleMuscleMicePlasma membrane4Early defectsLiverMain siteAdipocytes
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 Insulin Resistance in A-ZIP/F-1 Fatless Mice*
Kim J, Gavrilova O, Chen Y, Reitman M, Shulman G. Mechanism of Insulin Resistance in A-ZIP/F-1 Fatless Mice*. Journal Of Biological Chemistry 2000, 275: 8456-8460. PMID: 10722680, DOI: 10.1074/jbc.275.12.8456.Peer-Reviewed Original ResearchConceptsType 2 diabetesInsulin resistanceFatless miceInsulin actionTriglyceride contentA-ZIP/FDevelopment of diabetesLiver triglyceride contentHyperinsulinemic-euglycemic clampAccumulation of triglyceridesMuscle/liverWild-type littermatesInsulin receptor substrate-1Receptor substrate-1Partitioning of fatSubsequent impairmentDiabetesFat metabolismMiceFat tissueLiverInsulin signalingMuscleLatter tissueSubstrate-1Intramuscular Glycogen and Intramyocellular Lipid Utilization during Prolonged Exercise and Recovery in Man: A 13C and 1H Nuclear Magnetic Resonance Spectroscopy Study1
Krssak M, Petersen K, Bergeron R, Price T, Laurent D, Rothman D, Roden M, Shulman G. Intramuscular Glycogen and Intramyocellular Lipid Utilization during Prolonged Exercise and Recovery in Man: A 13C and 1H Nuclear Magnetic Resonance Spectroscopy Study1. The Journal Of Clinical Endocrinology & Metabolism 2000, 85: 748-754. PMID: 10690886, DOI: 10.1210/jcem.85.2.6354.Peer-Reviewed Original ResearchProlonged exerciseIMCL contentGlycogen contentBaseline valuesSoleus muscleMuscle glycogenMuscle groupsGreater muscle glycogen utilizationForearm musclesGlycogen concentrationLipid utilizationIntramyocellular lipid poolMuscle glycogen utilizationCalf muscle groupThigh muscle groupsIntramyocellular glycogenNonexercising muscleIntramuscular glycogenGlycogen depletionGlycogen utilizationTime of exhaustionLeg musclesThigh musclesSubmaximal intensitiesMuscle