title: Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance.
abstract: Insulin resistance in skeletal muscle is a characteristic feature of diabetes mellitus type 2 (DM2). Several lines of circumstantial evidence suggest that reduced mitochondrial oxidative phosphorylation capacity in skeletal muscle is a primary defect causing insulin resistance and subsequent development of DM2. We have now experimentally tested this hypothesis by characterizing glucose homeostasis in tissue-specific knockout mice with progressive respiratory chain dysfunction selectively in skeletal muscle. Surprisingly, these knockout mice are not diabetic and have an increased peripheral glucose disposal when subjected to a glucose tolerance test. Studies of isolated skeletal muscle from knockout animals show an increased basal glucose uptake and a normal increase of glucose uptake in response to insulin. In summary, our findings indicate that mitochondrial dysfunction in skeletal muscle is not a primary etiological event in DM2.
authors.affiliation: Department of Laboratory Medicine, Karolinska Insitutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wredenberg
authors.forename: Christoph
authors.initials: C
authors.lastname: Freyer
authors.forename: Marie E
authors.initials: ME
authors.lastname: Sandström
authors.forename: Abram
authors.initials: A
authors.lastname: Katz
authors.forename: Rolf
authors.initials: R
authors.lastname: Wibom
authors.forename: Håkan
authors.initials: H
authors.lastname: Westerblad
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D004579:Electron Transport; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose