ausblenden:
Schlagwörter:
AMP-Activated Protein Kinases
Animals
Electron Transport
Enzyme Activation
Glucose/metabolism
Glucose Tolerance Test
Glucose Transport Proteins, Facilitative/metabolism
Insulin Resistance/*physiology
Mice
Mice, Transgenic
Mitochondria/metabolism
Multienzyme Complexes/metabolism
Muscle, Skeletal/*metabolism
Protein-Serine-Threonine Kinases/metabolism
Zusammenfassung:
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.
