Rapid regulation of plasma membrane insulin receptors.

Injection IP of insulin at a dosage of 1 microgram/g body weight into normal rats produced a rapid rise in serum insulin levels from < 1 to 298 ng/ml, and a rapid decrease in specific 125I-insulin binding to its receptors in purified liver plasma membranes. A fall in binding was seen as early as 10 minutes after injection and binding remained decreased for up to 60 min. At 10 min, 125I-insulin binding had fallen to 59% of controls; in contrast, 125I-glucagon binding remained unchanged. Extraction of these plasma membrane followed by radioimmunoassay for insulin did not reveal appreciable amounts of exogenous insulin. The 125I-insulin dissociation rate from plasma membranes of control and insulin treated rats was the same, also indicating a lack of exogenous insulin. Scatchard analyses indicated that the decreased binding seen after insulin injection was due primarily to a change in the number of insulin receptors and not their affinity. These studies suggest, therefore, that high doses of insulin in vivo can rapidly regulate the number of plasma membrane insulin receptors in liver.