Mechanism of glucocorticoid-induced increase in insulin receptors of cultured human lymphocytes.
Glucocorticoids increase the number of insulin receptors in cultured human lymphocytes. This effect is specific for the insulin receptor as growth hormone receptor concentration decreases. The effect is time-dependent, dose-dependent over the physiologic concentration range of glucocorticoid, reversible, and appears to be mediated via specific glucocorticoid receptors. Protein synthesis and glycosylation are required as the effect is inhibited by actinomycin D, puromycin, cycloheximide, and tunicamycin. Isolated solubilized plasma membranes, as well as solubilized whole cells from glucocorticoid-treated lymphocytes, show the same increase in insulin receptors as do intact cells. The glucocorticoid-induced receptors are immunologically indistinguishable from control when precipitated by anti-receptor antibody. Glucocorticoids do not stabilize existing receptors since the degradation rate of receptors is actually increased. Regulation of the insulin receptor by insulin is independent of the steroid effect. However, there is a right-ward shift of the dose-response curve for "down regulation" by insulin in the presence of glucocorticoid. We conclude that glucocorticoids increase the number of insulin receptors in cultured human lymphocytes by increasing the synthesis of new receptors. This represents the first induction of insulin receptor synthesis by a pharmacologic agent.
D001667:Binding, Competitive; D002460:Cell Line; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*
D005938:Glucocorticoids; D007328:Insulin; C008147:insulin, iodo-; D011972:Receptor, Insulin