Insulin-induced loss of the insulin receptor in IM-9 lymphocytes. A biological process mediated through the insulin receptor.

Abstract

Exposure of cultured lymphocytes of the IM-9 line to insulin results in a rapid, time-dependent reduction in the number of insulin receptors to a new steady state concentration. Both the rate of loss and the net loss of receptors were directly related to the ambient insulin concentration. The insulin-induced loss of receptors was mediated by binding of insulin to the receptor itself; insulins, which varied 200-fold in biopotency, produced receptor loss in direct proportion to the ability of each insulin to occupy the receptor. The residual insulin receptors were normal following insulin-mediated receptor loss by a variety of sensitive binding criteria. While insulin binding to its receptors was a necessary condition to induce receptor loss, it was not sufficient. Thus, reduction in the temperature of the preincubation from 37 degrees C to 20 degrees C (which enhanced the total amount of insulin bound to the receptor) abolished the loss of insulin receptors. Likewise, cycloheximide prevented the insulin-induced loss of receptors. Furthermore, turkey erythrocytes, which lack active macromolecular synthesis, had no change in the concentration of insulin receptors when exposed to insulin for similar periods. Interestingly, the turkey erythrocytes, when exposed to insulin or to proinsulin, showed a time- and concentration-dependent increase in the affinity of the insulin receptor over a restricted part of the insulin-binding isotherm, which was reversed over a period of several hours following removal of hormone. The insulin-mediated decrease in receptor number on IM-9 lymphocytes was reversible. Following removal of insulin from the growth medium, about one-half of the receptors were restored within 10 h and the full complement of insulin receptors was restored within 24 h. Cycloheximide prevented restoration of the insulin receptor.