title: Mechanisms of muscle insulin resistance in obese individuals.
abstract: We previously reported that insulin resistance in skeletal muscle of obese individuals was associated with decreases in insulin signal transduction and tyrosine kinase activity of the insulin receptor. Herein is reviewed the recently published data supporting the hypothesis that protein kinase C (PKC) phosphorylates the insulin receptor on serine/threonine residues to decrease tyrosine kinase activity and cause insulin resistance. Treatment of insulin receptors from obese subjects with alkaline phosphatase restored tyrosine kinase activity, suggesting that the reduced activity was a result of hyperphosphorylation of the receptor. Incubating human muscle fiber strips with PKC inhibitors restored insulin action in muscle of obese patients, while activating PKC with a phorbol ester caused insulin resistance in muscle from lean control patients. The beta isoform of PKC was elevated in muscle of obese, insulin-resistant patients. These data are consistent with the hypothesis that elevated PKC activity may cause insulin resistance by phosphorylating the insulin receptor to decrease tyrosine kinase activity.
authors.affiliation: Department of Biochemistry, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Dohm
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004195:Disease Models, Animal; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D011493:Protein Kinase C