Effects of hypercortisolemia and diabetes on skeletal muscle insulin receptor function in vitro and in vivo.
Activation of skeletal muscle insulin receptor tyrosine kinase in vitro and in vivo was studied in two rat models of insulin resistance: insulinopenic diabetes and hypercortisolemia. In control rats, intravenous insulin administration resulted in dose-dependent in vivo activation of the muscle insulin receptor kinase towards histone H2b. Half-maximal and maximal activation were observed 5 min after injecting 0.1 and 0.5 U insulin/100 g, respectively. Diabetes (7 days) induced with streptozotocin did not affect insulin binding affinity of solubilized muscle receptors but depressed receptor kinase activation in vivo by 52 or 40% after intravenous insulin administration (0.1 or 2 U/100 g, respectively). Cortisone treatment (5 days) resulting in weight loss, hyperglycemia, and hyperinsulinemia did not affect the number, insulin binding affinity, or kinase activity of solubilized receptors activated with insulin in vitro or in vivo. It is concluded that impaired insulin receptor tyrosine kinase activation was demonstrated in vivo in rats with insulinopenic diabetes and that glucocorticoid-induced insulin resistance probably reflects postreceptor defect(s) in muscle.
Block
N E
NE
Department of Medicine and Biochemistry, Medical University of South Carolina, Charleston 29425.
Buse
M G
MG
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003348:Cortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D009132:Muscles / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D006657:Histones; D007328:Insulin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D003348:Cortisone; D006854:Hydrocortisone