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
2020
Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity
O'Mara A, Johnson J, Linderman J, Brychta R, McGehee S, Fletcher L, Fink Y, Kapuria D, Cassimatis T, Kelsey N, Cero C, Sater Z, Piccinini F, Baskin A, Leitner B, Cai H, Millo C, Dieckmann W, Walter M, Javitt N, Rotman Y, Walter P, Ader M, Bergman R, Herscovitch P, Chen K, Cypess A. Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. Journal Of Clinical Investigation 2020, 130: 2209-2219. PMID: 31961826, PMCID: PMC7190915, DOI: 10.1172/jci131126.Peer-Reviewed Original ResearchConceptsBAT metabolic activityIntravenous glucose tolerance testGlucose tolerance testΒ3-AR agonistInsulin sensitivityTolerance testMetabolic diseasesObesity-related metabolic diseasesWhite adipose tissue lipolysisBrown adipose tissue thermogenesisOpen-label studyTotal bile acidsHuman brown fatHigher insulin sensitivityAdipose tissue lipolysisAdipose tissue thermogenesisPET/CTΒ3-adrenergic receptor agonistIntramural Research ProgramChronic pharmacological stimulationMetabolic activityMirabegron therapyMirabegron treatmentPrimary endpointSecondary endpoints