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
2014
Muscle-specific activation of Ca2+/calmodulin-dependent protein kinase IV increases whole-body insulin action in mice
Lee HY, Gattu AK, Camporez JP, Kanda S, Guigni B, Kahn M, Zhang D, Galbo T, Birkenfeld AL, Jornayvaz FR, Jurczak MJ, Choi CS, Yan Z, Williams RS, Shulman GI, Samuel VT. Muscle-specific activation of Ca2+/calmodulin-dependent protein kinase IV increases whole-body insulin action in mice. Diabetologia 2014, 57: 1232-1241. PMID: 24718953, PMCID: PMC5634138, DOI: 10.1007/s00125-014-3212-1.Peer-Reviewed Original ResearchConceptsMitochondrial contentDependent protein kinaseDependent protein kinase IVSkeletal muscleInsulin actionMuscle mitochondrial contentInsulin-stimulated glucose uptakeMuscle-specific activationΓ coactivator 1αGlucose uptakePhosphorylation of AktSkeletal muscle insulin actionProtein kinaseOxidative type IMitochondrial biogenesisKinase IVMuscle insulin actionGLUT4 proteinGlucose metabolismInsulin-stimulated whole-body glucose uptakePleiotropic effectsWhole-body glucose uptakeCAMK4Coactivator 1αWhole-body insulin action
2013
Cellular Mechanisms by Which FGF21 Improves Insulin Sensitivity in Male Mice
Camporez JP, Jornayvaz FR, Petersen MC, Pesta D, Guigni BA, Serr J, Zhang D, Kahn M, Samuel VT, Jurczak MJ, Shulman GI. Cellular Mechanisms by Which FGF21 Improves Insulin Sensitivity in Male Mice. Endocrinology 2013, 154: 3099-3109. PMID: 23766126, PMCID: PMC3749479, DOI: 10.1210/en.2013-1191.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, BrownAnimalsCells, CulturedDiet, High-FatDrug ImplantsEnergy MetabolismFibroblast Growth FactorsGlucose IntoleranceHumansInfusions, SubcutaneousInsulin ResistanceIsoenzymesLipectomyLipid MetabolismLiverMaleMiceMice, Inbred C57BLMuscle, SkeletalProtein Kinase CProtein Kinase C-epsilonProtein Kinase C-thetaRecombinant ProteinsConceptsType 2 diabetesInsulin resistanceRegular chowInsulin sensitivityInsulin actionNonalcoholic fatty liver diseaseFibroblast growth factor 21Fatty liver diseasePeripheral insulin sensitivityEffects of FGF21HFD-fed miceGrowth factor 21High-fat dietCellular mechanismsWild-type miceWhite adipose tissueMuscle insulin resistanceMuscle ceramide contentProtein kinase Cε activationFGF21 administrationLiver diseaseFactor 21Male miceNovel therapiesAdipose tissueCellular 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
2011
Influence of the Hepatic Eukaryotic Initiation Factor 2α (eIF2α) Endoplasmic Reticulum (ER) Stress Response Pathway on Insulin-mediated ER Stress and Hepatic and Peripheral Glucose Metabolism*
Birkenfeld AL, Lee HY, Majumdar S, Jurczak MJ, Camporez JP, Jornayvaz FR, Frederick DW, Guigni B, Kahn M, Zhang D, Weismann D, Arafat AM, Pfeiffer AF, Lieske S, Oyadomari S, Ron D, Samuel VT, Shulman GI. Influence of the Hepatic Eukaryotic Initiation Factor 2α (eIF2α) Endoplasmic Reticulum (ER) Stress Response Pathway on Insulin-mediated ER Stress and Hepatic and Peripheral Glucose Metabolism*. Journal Of Biological Chemistry 2011, 286: 36163-36170. PMID: 21832042, PMCID: PMC3196114, DOI: 10.1074/jbc.m111.228817.Peer-Reviewed Original ResearchConceptsHepatic glucose productionInsulin sensitivityInsulin resistanceCaloric excessER stressHigh-fat diet-fed miceBasal plasma glucose concentrationsGlucose productionIGFBP-3 levelsHepatic ERPeripheral glucose metabolismTissue insulin sensitivityDiet-fed miceHepatic lipid accumulationHigh-fat dietHyperinsulinemic-euglycemic clampHepatic insulin sensitivityInfusion of insulinPlasma glucose concentrationEndoplasmic reticulum stress response pathwayEndoplasmic reticulum stressInsulin-stimulated muscleIGFBP-3Fat dietMuscle glucose
2007
Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance
Choi CS, Fillmore JJ, Kim JK, Liu ZX, Kim S, Collier EF, Kulkarni A, Distefano A, Hwang YJ, Kahn M, Chen Y, Yu C, Moore IK, Reznick RM, Higashimori T, Shulman GI. Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance. Journal Of Clinical Investigation 2007, 117: 1995-2003. PMID: 17571165, PMCID: PMC1888566, DOI: 10.1172/jci13579.Peer-Reviewed Original ResearchMeSH KeywordsAgingAMP-Activated Protein KinasesAnimalsEnzyme ActivationGene Expression RegulationHormonesHumansInsulinInsulin ResistanceIon ChannelsIsoenzymesLipid MetabolismMaleMiceMice, TransgenicMitochondrial ProteinsMultienzyme ComplexesMuscle, SkeletalProtein Kinase CProtein Kinase C-thetaProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktUncoupling Protein 3Weight GainConceptsFat-induced insulin resistanceInsulin resistanceSkeletal muscleType 2 diabetes mellitusProtein 3IRS-2-associated PI3K activityHigh-fat dietType 2 diabetesHepatic insulin resistanceWild-type miceInsulin-stimulated glucose uptakeExcellent therapeutic targetInsulin-stimulated insulin receptor substrate 1Fatty acid metabolitesSerine kinase cascadeInsulin receptor substrate-1Intramyocellular fatDiabetes mellitusSkeletal muscle protectsReceptor substrate-1Therapeutic targetTransgenic miceAcid metabolitesPI3K activityGlucose uptake