Pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus: candidates for a signal transmitter defect causing insulin resistance of the skeletal muscle.
Insulin resistance of skeletal muscle, liver and fat combined with an abnormality of insulin secretion characterizes Type 2 (non-insulin-dependent) diabetes mellitus. There is increasing evidence that the insulin resistance of the skeletal muscle plays a key role early in the development of Type 2 diabetes. As a consequence recent research efforts have focussed on the characterization of insulin signal transduction elements in the muscle which are candidates for a localization of a defect causing insulin resistance i.e. the insulin receptor, phosphatases related to insulin action, glycogen synthase and the glucose transporters. In this review we attempt to summarize present knowledge about abnormalities of these systems in skeletal muscle of Type 2 diabetic and pre-diabetic individuals. We try to classify abnormalities as secondary events or as candidates for putative primary molecular defects which might initiate the development of insulin resistance as early as in the "pre-diabetic" state.
Institute for Diabetes Research, Krankenhaus München-Schwabing, Germany.
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Mehnert
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D006006:Glycogen Synthase / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009132:Muscles / Q000503:physiopathology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011236:Prediabetic State / Q000503:physiopathology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000502:physiology*; D015398:Signal Transduction
D009004:Monosaccharide Transport Proteins; D006006:Glycogen Synthase; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D010744:Phosphoric Monoester Hydrolases