Autophosphorylation and kinase activity of insulin receptor in diabetic rats.
Insulin resistance is observed in insulin-deficient diabetic states in spite of an increase in insulin binding to its target cells. To characterize this type of insulin resistance, autophosphorylation and kinase activity of the insulin receptor on liver was studied with streptozotocin (STZ)-induced and BB diabetic rats. Insulin binding capacity was increased in proportion to the severity of the diabetic state in the STZ rat. In the diabetic BB rat, the insulin binding capacity was also increased, and this was partially normalized by insulin treatment. By contrast, insulin-stimulated autophosphorylation of the beta-subunit of the insulin receptor was decreased in proportion to the severity of the diabetic state in the STZ rat. Peptide mapping by reverse-phase high-performance liquid chromatography revealed a decrease in labeling at all sites of autophosphorylation. Kinase activity of the insulin receptor to exogenous substrates was also decreased in proportion to the diabetic state. In the BB rat, autophosphorylation and kinase activity of the insulin receptor were both decreased in the diabetic state and partially normalized by insulin treatment. In addition to the beta-subunit of insulin receptor, a 170 kdalton phosphotyrosine-containing protein was also identified in the glycoprotein fraction of liver. Although the phosphorylation of this protein was not insulin dependent, it was decreased markedly in the diabetic state. This protein is immunologically distinct from the insulin receptor, but is rich in phosphotyrosine. Based on its size and phosphotyrosine content, this protein may be the epidermal growth factor receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D007328:Insulin; D010446:Peptide Fragments; D019000:Phosphotyrosine; D014443:Tyrosine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin