Insulin binding to target cells (general survey, problems and results in spontaneous obesity)

Following Yalow and Berson's basic research on the binding of polypeptide hormones to plasma proteins, an integrated picture of hormone-receptor interaction and biological activity has been proposed for insulin in experimental models and in man. The extracellular interaction of the insulin molecule with the cell membrane structure modifies the intracellular metabolism, and it has been suggested that this occurs through the activation of a second messenger or the transduction of an insulin fragment into the cell. The use of monoiodoinsulin has made it possible to perform a series of experiments on cells isolated from the blood (monocytes) or from the tissues (adipocytes) and on plasma membranes prepared by ultracentrifugation. The existence of specific receptor sites for insulin in all cases, both in animals and in man, has been confirmed by mathematical analysis of the binding curves; their non-linear course, as plotted by Scatchard's method, may depend on negative cooperation or on different classes of receptor. From an evaluation of recent studies on human obesity, particularly on adipocytes and circulating monocytes, a new approach to the problem of 'insulin resistance' in obesity has been proposed, and this has shown that a reduction in the number of receptors on the target cells may contribute to peripheral insulin insensitivity. This phenomenon, which seems to be characteristic of the static phase of obesity, is reversible during fasting or weight reduction and may be a compensatory mechanism for hyperinsulinaemia. These results are an example of the significance and applicability of the experimental method of detecting insulin binding to target cells, and suggest a wide application in different endocrinological fields.