Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin-diabetic rats.
It has been documented that streptozotocin-induced diabetes in rats is associated with diminished effects of insulin despite increased insulin binding to its receptor. This paradox led us to examine whether any alterations of insulin receptor-kinase activities occur in this type of insulin resistance. Insulin binding capacity/mg of protein of solubilized, wheat germ agglutinin-purified preparations from livers was increased by 1.8-fold in the streptozotocin (65 mg/kg) diabetic rats. This increase was associated with a parallel increase in receptor protein as measured by an immunoblotting method using anti-insulin receptor antibody. Moreover, no apparent change was observed in the stoichiometry of alpha and beta subunits of the insulin receptor between diabetic and control rats. Insulin-stimulated (10(-7) M) phosphorylation of the beta subunit of the insulin receptor was decreased by 40% in diabetic rats when equal quantities of insulin binding capacity were compared. Phosphorylation of an exogenously added synthetic peptide (similar in sequence to the tyrosine phosphorylation site in pp60src) by the insulin receptor-kinase was also decreased by 25% in diabetic rats. These abnormalities were partially restored by in vivo insulin treatment. These data suggest that diminished insulin receptor autophosphorylation and kinase activity could provide a possible mechanism for the "post-binding insulin resistance" in diabetic rats.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D007163:Immunosorbent Techniques; D007328:Insulin / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin; D013997:Time Factors; D014909:Wheat Germ Agglutinins
D007328:Insulin; D037102:Lectins; D014909:Wheat Germ Agglutinins; D011494:Protein Kinases; D011972:Receptor, Insulin