The insulin receptor

Abstract

The insulin receptor is a glycoprotein with a molecular weight in the order of 300,000. There are probably two pairs of subunits joined together by disulphide bonds. The distribution of receptors appears to be tissue-specific. On liver plasma membranes they are found predominantly as singletons, whereas on adipocytes they occur mainly in groups. The groups of receptors are held together by disulphide bonds, but these are different from the bonds holding the subunits together. When insulin binds to the receptor, the hormone-receptor complex is internalised in pinocytotic invaginations in the adipocyte, and in coated pits in fibroblasts. Half the receptors are transported to lysosomes where they are degraded, and the other half are recycled to the cell surface presumably for further re-utilisation. Obese patients and those with type II diabetes have in common both a reduced number of insulin receptors and a post-receptor defect. However the degree of insulin resistance in type II diabetes cannot be accounted for on the basis of obesity alone. Moreover many type II diabetics are not obese. The insulin receptor is also altered in certain physiological states. Fasting and exercise lead to increased binding of insulin to its receptor. Pregnancy, on the other hand, may either increase or reduce binding. The effects of glucocorticoids are heterogeneous, and it is probable that the insulin resistance they induce is post-receptor in nature. Auto-antibodies to the insulin receptor is a rare cause of severe insulin-resistant diabetes, but the condition has given considerable insight into the nature of the insulin receptor.(ABSTRACT TRUNCATED AT 250 WORDS)