Abnormal insulin receptor tyrosine kinase activity in kidney basolateral membranes from non-insulin-dependent diabetic rats.
Neonatal rats that receive injections of streptozotocin develop insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). Insulin resistance precedes development of overt diabetes, and some insulin bioeffects are known to be impaired at the postreceptor level in several target tissues of this rat model. We studied a possible contribution of altered insulin receptor function to the impaired insulin action in these animals. Activity of the insulin-sensitive tyrosine kinase of receptors from kidney cortical basolateral membranes (BLMs) obtained from these nonobese, normoinsulinemic, insulin-resistant rats was examined at the age of 5 weeks (before overt hyperglycemia developed) and at 10 weeks (after NIDDM was fully manifested). In experimental animals, at both 5 and 10 weeks, binding of insulin labeled with iodine 125 to crude kidney BLM was higher than in their control littermates. However, no such difference was found with insulin binding to purified insulin receptors from BLM. The insulin receptor, tyrosine kinase activity (TKA), to an exogenous substrate was higher in diabetic tissue both at basal condition and after insulin stimulation at both 5 and 10 weeks of age. Autophosphorylation of the beta-subunit of the insulin receptor and the proportion of tyrosine-phosphorylated ("active") insulin receptors from BLM was also higher in diabetic rats. There was an age-related increase in the receptor TKA between 5 and 10 weeks in both diabetic and control animals. A 24-hour fast normalized insulin binding and nearly abolished the difference in TKA of the BLM receptors from 5-week-old insulin-resistant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Grunberger
G
G
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI.
Nagy
K
K
Rempinski
D
D
Levy
J
J
D000818:Animals; D001485:Basement Membrane / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D006943:Hyperglycemia / Q000201:enzymology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D007668:Kidney / Q000201:enzymology*; D008297:Male; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism
D007328:Insulin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin