Regulation of rat insulin-receptor kinase by glucose in vivo.
The effects of acute and chronic hyperglycemia on the kinase activity of insulin receptors in vivo were studied in the rat. Skeletal muscle-derived insulin receptors were isolated, with preservation of the in vivo phosphorylation state, from nondiabetic rats subjected to hyperinsulinemic clamps at either euglycemia (mean 5.2 mM) or hyperglycemia (14.4 mM) or from streptozocin-induced diabetic rats at euglycemia (5.1 mM) or hyperglycemia (14.2 mM). Kinase activity toward histone of insulin receptors from nondiabetic animals rendered hyperglycemic for 80-90 min was 50% higher than that of receptors from rats clamped at euglycemia (mean +/- SE 4.5 +/- 0.4 vs. 3.0 +/- 0.3 fmol of phosphate into histone, respectively, P less than 0.02), although kinase activity of receptors isolated from animals rendered diabetic for 10-14 days before hyperglycemic or euglycemic clamps showed no such effect. These results suggest that acute hyperglycemia may increase insulin-receptor kinase activity in vivo, possibly augmenting glucose disposal thereby, whereas the chronic hyperglycemia of diabetes mellitus results in metabolic derangements that nullify this effect.
Department of Medicine, University of British Columbia, Vancouver, Canada.
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Bryer-Ash
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006657:Histones / Q000378:metabolism; D006706:Homeostasis; D006943:Hyperglycemia / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D012016:Reference Values; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D006657:Histones; D007328:Insulin; D013004:Somatostatin; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin