title: Partial Disruption of Lipolysis Increases Postexercise Insulin Sensitivity in Skeletal Muscle Despite Accumulation of DAG.
abstract: Type 2 diabetes and skeletal muscle insulin resistance have been linked to accumulation of the intramyocellular lipid-intermediate diacylglycerol (DAG). However, recent animal and human studies have questioned such an association. Given that DAG appears in different stereoisomers and has different reactivity in vitro, we investigated whether the described function of DAGs as mediators of lipid-induced insulin resistance was dependent on the different DAG isomers. We measured insulin-stimulated glucose uptake in hormone-sensitive lipase (HSL) knockout (KO) mice after treadmill exercise to stimulate the accumulation of DAGs in skeletal muscle. We found that, despite an increased DAG content in muscle after exercise in HSL KO mice, the HSL KO mice showed a higher insulin-stimulated glucose uptake postexercise compared with wild-type mice. Further analysis of the chemical structure and cellular localization of DAG in skeletal muscle revealed that HSL KO mice accumulated sn-1,3 DAG and not sn-1,2 DAG. Accordingly, these results highlight the importance of taking the chemical structure and cellular localization of DAG into account when evaluating the role of DAG in lipid-induced insulin resistance in skeletal muscle and that the accumulation of sn-1,3 DAG originating from lipolysis does not inhibit insulin-stimulated glucose uptake.
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Annette Karen
authors.initials: AK
authors.lastname: Serup
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark Clamp Competency Center, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Thomas Junker
authors.initials: TJ
authors.lastname: Alsted
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas Børsting
authors.initials: AB
authors.lastname: Jordy
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.affiliation: Department of Experimental Medical Science, Lund University Biomedical Centre, Lund, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Holm
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark bkiens@nexs.ku.dk.
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004075:Diglycerides / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008066:Lipolysis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D002787:Sterol Esterase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D007328:Insulin; D002787:Sterol Esterase; D005947:Glucose