Demonstration by radiation inactivation that insulin alters the structure of the insulin receptor in rat liver membranes.
Using the technique of radiation inactivation we have previously shown that the insulin receptor in rat liver membranes is composed of at least two functional components: an insulin binding component and a component which acts as an affinity regulator ((1980) J. Biol. Chem. 255, 3412-3419). In the present study, we have used this technique to examine whether insulin alters the size or structure of the insulin receptor. When insulin is bound to its receptor in liver membranes before radiation, there is a marked change in the inactivation profile. Analysis of the results of indicated that insulin binding to its receptor caused a decrease in the functional size of the insulin binding component from 115,000 to 76,000 and also diminished the interaction between the binding and regulatory components. The magnitude of these effects depended on the insulin concentration, and analogues of insulin with reduced receptor affinity show a reduced effect. Under these conditions, there was no change in the apparent size of the affinity regulator (about 260,000). These data suggest that the interaction of insulin with its receptor in situ produces a change in receptor structure which may be important in signal transmission.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008970:Molecular Weight; D011384:Proinsulin / Q000494:pharmacology; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects
D007328:Insulin; C008147:insulin, iodo-; D011384:Proinsulin; D011972:Receptor, Insulin