The mechanisms of up-regulation of the hepatic insulin receptor in hypoinsulinemic diabetes mellitus.
The mechanism underlying the increased insulin binding found in hepatic plasma membranes from streptozotocin-diabetic rats was evaluated by measuring insulin binding to intact and Triton X-100-soluble extracts of plasma membranes prepared from the livers of control rats and rats administered streptozotocin (85 mg/kg). In addition, to assess whether the cellular content of hepatic insulin receptors is also increased in diabetic animals, we measured insulin-binding activity in intact and soluble extracts of total hepatic cellular membrane preparations (100,000 X g cellular pellets). The data indicate that while insulin binding is increased (52 +/- 3%) in intact hepatic plasma membranes from diabetic rats compared to control rats, there is no comparable increase in insulin binding in intact total cellular membranes or in Triton X-100-soluble extracts of plasma membranes or total cellular membranes. We therefore conclude that the enhanced insulin binding found in the livers of diabetic rats is the result of a local redistribution of plasma membrane insulin receptors from cryptic to exposed sites. Finally, the data suggest the presence of a negative modulator of insulin-binding affinity in intact plasma and total cellular membranes.
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*
D007328:Insulin; C008147:insulin, iodo-; D011972:Receptor, Insulin