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
2023
191-OR: Deletion of the Type 2 Diabetes Candidate Gene SLC16A11 Reduces Peripheral Insulin Sensitivity in Mice
EL-AGROUDY N, SCHUMANN T, KURZBACH A, SANCAR G, SANDFORTH L, HERRMANN C, SHULMAN G, BIRKENFELD A. 191-OR: Deletion of the Type 2 Diabetes Candidate Gene SLC16A11 Reduces Peripheral Insulin Sensitivity in Mice. Diabetes 2023, 72 DOI: 10.2337/db23-191-or.Peer-Reviewed Original ResearchDb/db miceOb/obInsulin sensitivityDb miceMRNA expressionWhole-body insulin sensitivitySkeletal muscle insulin sensitivitySkeletal muscle insulin resistanceSkeletal musclePeripheral insulin sensitivityTreatment of T2D.Hyperinsulinemic-euglycemic clampLiver fat contentGlucose infusion rateMuscle insulin sensitivityMuscle insulin resistanceHepatic glucose productionHepatic mitochondrial functionWT littermate mice
2022
Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice
Gaspar R, Lyu K, Hubbard B, Leitner B, Luukkonen P, Hirabara S, Sakuma I, Nasiri A, Zhang D, Kahn M, Cline G, Pauli J, Perry R, Petersen K, Shulman G. Distinct subcellular localisation of intramyocellular lipids and reduced PKCε/PKCθ activity preserve muscle insulin sensitivity in exercise-trained mice. Diabetologia 2022, 66: 567-578. PMID: 36456864, PMCID: PMC11194860, DOI: 10.1007/s00125-022-05838-8.Peer-Reviewed Original ResearchConceptsProtein kinase CsSubcellular compartmentsDistinct subcellular localisationMuscle insulin sensitivityMultiple subcellular compartmentsInsulin receptor kinaseNovel protein kinase CsActivation of PKCεSubcellular localisationPKCθ translocationReceptor kinasePlasma membraneSubcellular distributionTriacylglycerol contentCrucial pathwaysIntramuscular triacylglycerol contentRC miceDiacylglycerolConclusions/interpretationThese resultsPKCεPM compartmentPhosphorylationMuscle triacylglycerol contentSkeletal muscleRecent findings
2021
501-P: Lower Plasma Membrane Sn-1,2-Diacylglycerol Content and PKCepsilon/theta Activity Explain the Athlete’s Paradox
GASPAR R, LYU K, HUBBARD B, LEITNER B, LUUKKONEN P, HIRABARA S, SAKUMA I, NASIRI A, ZHANG D, KAHN M, CLINE G, PAULI J, PERRY R, PETERSEN K, SHULMAN G. 501-P: Lower Plasma Membrane Sn-1,2-Diacylglycerol Content and PKCepsilon/theta Activity Explain the Athlete’s Paradox. Diabetes 2021, 70 DOI: 10.2337/db21-501-p.Peer-Reviewed Original ResearchHigh-fat diet feedingMuscle insulin sensitivityEX miceInsulin sensitivitySpouse/partnerGlucose toleranceIntramyocellular lipidsAthlete's paradoxRC micePKCθ translocationHyperinsulinemic-euglycemic clamp studiesGilead SciencesJanssen ResearchMuscle TAG contentMuscle triglyceride contentMale C57BL/6J miceImproved glucose toleranceNovo NordiskMuscle insulin resistanceNovo Nordisk FoundationBoehringer Ingelheim PharmaceuticalsChow feedingHFD groupHFD miceInsulin resistance
2018
Metabolic Inflexibility Revisited—Muscle Substrate Oxidation Is Mechanistically Dissociated from Muscle Insulin Resistance in Rats
SONG J, PERRY R, MUNK A, ZHANG Y, ZHANG D, SHULMAN G. Metabolic Inflexibility Revisited—Muscle Substrate Oxidation Is Mechanistically Dissociated from Muscle Insulin Resistance in Rats. Diabetes 2018, 67 DOI: 10.2337/db18-240-lb.Peer-Reviewed Original ResearchInsulin-resistant ratsMuscle insulin resistanceHigh-fat dietResistant ratsInsulin resistanceNormal ratsSoleus muscleLipid-induced muscle insulin resistanceSkeletal muscle insulin resistancePeripheral glucose metabolismHyperinsulinemic-euglycemic clampPathogenesis of obesityMuscle insulin sensitivityGlucose oxidationMuscle glucose transportAcute infusionPyruvate dehydrogenase fluxSubstrate oxidationFat dietMuscle glucoseInsulin sensitivityAcute modulationGlucose metabolismFat oxidationTissue-specific indices
2000
Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice
Gavrilova O, Marcus-Samuels B, Graham D, Kim J, Shulman G, Castle A, Vinson C, Eckhaus M, Reitman M. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. Journal Of Clinical Investigation 2000, 105: 271-278. PMID: 10675352, PMCID: PMC377444, DOI: 10.1172/jci7901.Peer-Reviewed Original ResearchConceptsA-ZIP/FLipoatrophic diabetesAdipose tissueNear-physiological amountsMuscle insulin sensitivityLack of fatLipoatrophic miceInsulin levelsHepatic steatosisInsulin resistanceInsulin sensitivitySevere formFFA levelsDiabetesDonor fatTransplantationBeneficial effectsEndocrine communicationSubcutaneous sitesMiceSurgical implantationAdipose physiologyHyperglycemiaFatTissue