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, 73: 2055-2064. PMID: 39264820, PMCID: PMC11579410, 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-DAGMuscleSkeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α
Liu B, Xie D, Huang X, Jin S, Dai Y, Sun X, Li D, Bennett A, Diano S, Huang Y. Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α. Diabetologia 2024, 67: 724-737. PMID: 38216792, PMCID: PMC10904493, DOI: 10.1007/s00125-023-06073-5.Peer-Reviewed Original ResearchConceptsTen-eleven translocationMuscle insulin sensitivityRNA-seqPGC-1aRegulation of muscle insulin sensitivityType 2 diabetesAnalysis of RNA-seqResponse to environmental cuesGenome-wide expression profilingWild-typeHFD-fedHFD-induced insulin resistanceHigh-fat diet (HFD)-inducedExpression levelsMaintenance of glucoseSkeletal muscle insulin sensitivityAccession numbersSkeletal muscleEnhanced glucose toleranceFamily dioxygenasesMitochondrial respirationSkeletal muscle of humansEnvironmental cuesMitochondrial functionBiological processes
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
2018
Predictive Accuracy of Surrogate Indices for Hepatic and Skeletal Muscle Insulin Sensitivity
Muniyappa R, Tella S, Sortur S, Mszar R, Grewal S, Abel B, Auh S, Chang D, Krakoff J, Skarulis M. Predictive Accuracy of Surrogate Indices for Hepatic and Skeletal Muscle Insulin Sensitivity. Journal Of The Endocrine Society 2018, 3: 108-118. PMID: 30675598, PMCID: PMC6299271, DOI: 10.1210/js.2018-00206.Peer-Reviewed Original ResearchOral glucose tolerance testInsulin sensitivitySurrogate indexGlucose clampDegrees of glucose toleranceInsulin sensitivity/resistance indicesHyperinsulinemic-euglycemic glucose clampGlucose tolerance testTritiated glucose infusionCross-sectional studyOGTT-derivedHepatic insulin sensitivityClinical studiesTolerance testGlucose tolerancePredicting insulin sensitivityMuscle insulin sensitivityGlucose infusionSkeletal muscle insulin sensitivityIndices of muscleSurrogate indicatorClampH19 lncRNA Promotes Skeletal Muscle Insulin Sensitivity in Part by Targeting AMPK
Geng T, Liu Y, Xu Y, Jiang Y, Zhang N, Wang Z, Carmichael GG, Taylor HS, Li D, Huang Y. H19 lncRNA Promotes Skeletal Muscle Insulin Sensitivity in Part by Targeting AMPK. Diabetes 2018, 67: db180370. PMID: 30201684, PMCID: PMC6198334, DOI: 10.2337/db18-0370.Peer-Reviewed Original ResearchConceptsMuscle insulin sensitivityEnergy sensor AMPKUnknown physiological functionImportant downstream effectorWhole-body energy metabolismCellular energy sensor AMPKEpigenetic mechanismsMuscle insulin resistanceDownstream effectorsAMPK activationMitochondrial biogenesisSystemic glucose homeostasisSkeletal muscle insulin sensitivityPhysiological functionsImportant regulatorAMPKInsulin-resistant human subjectsDUSP27Energy metabolismH19H19 expressionMuscle cellsSkeletal muscleGlucose uptakePivotal roleMetabolic 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
2016
The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women
Horst K, Versteeg RI, Gilijamse PW, Ackermans MT, Heijboer AC, Romijn JA, la Fleur SE, Trinko R, DiLeone RJ, Serlie MJ. The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women. Diabetes & Metabolism 2016, 42: 416-423. PMID: 27262368, DOI: 10.1016/j.diabet.2016.04.011.Peer-Reviewed Original ResearchConceptsVitamin D deficiencyObese womenInsulin actionD deficiencyVitamin DInsulin resistanceInsulin sensitivityGlucose metabolismEuglycaemic–hyperinsulinaemic clamp studiesActive vitamin D metaboliteBasal endogenous glucose productionObesity-related insulin resistanceTissue-specific insulin actionObesity-induced metabolic diseasesTissue-specific insulin sensitivitySkeletal muscle insulin sensitivityBody mass indexVitamin D metabolitesTotal body fatMuscle insulin sensitivityEndogenous glucose productionBaseline characteristicsSerum levelsMass indexD levels
2013
Cellular Mechanism by Which Estradiol Protects Female Ovariectomized Mice From High-Fat Diet-Induced Hepatic and Muscle Insulin Resistance
Camporez JP, Jornayvaz FR, Lee HY, Kanda S, Guigni BA, Kahn M, Samuel VT, Carvalho CR, Petersen KF, Jurczak MJ, Shulman GI. Cellular Mechanism by Which Estradiol Protects Female Ovariectomized Mice From High-Fat Diet-Induced Hepatic and Muscle Insulin Resistance. Endocrinology 2013, 154: 1021-1028. PMID: 23364948, PMCID: PMC3578999, DOI: 10.1210/en.2012-1989.Peer-Reviewed Original ResearchConceptsEstrogen replacement therapyOVX miceMuscle insulin sensitivityMuscle insulin resistanceInsulin resistanceInsulin sensitivityReplacement therapyHigh-fat diet feedingWhole-body insulin resistanceWhole-body insulin sensitivityFemale ovariectomized miceEctopic lipid depositionWhole-body energy expenditureType 2 diabetesEnergy expenditureWeeks of ageWhole-body energy homeostasisProtein kinase Cε activationHepatic DAG contentLivers of shamPostmenopausal womenSham miceOvariectomized miceGlucose toleranceE2 treatment
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
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