Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance.
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.
Wredenberg
Anna
A
Department of Laboratory Medicine, Karolinska Insitutet, Karolinska University Hospital, Stockholm, Sweden.
Freyer
Christoph
C
Sandström
Marie E
ME
Katz
Abram
A
Wibom
Rolf
R
Westerblad
Håkan
H
Larsson
Nils-Göran
NG
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
D051246:Glucose Transport Proteins, Facilitative; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose