Secretion, Fates and Actions of Insulin and Related Products

Abstract

It is not known whether the insulin secreted by diabetics is normal in all regards. In these subjects there are abnormalities with respect to the rate, amount, and duration of insulin release produced by certain agents. Insulin is rapidly distributed throughout the body, but more information is required regarding its intracellular distribution in different tissues, including comparisons in diabetics with normals. Insulin is a powerful hormone that influences, directly or indirectly, the activities of every tissue of the body including generation and storage of energy and regulation of its relase and utilization. It exerts pronounced influences upon cell structure, growth, and proliferation. It markedly stimulates the following: synthesis of DNA, RNA, and protein; oxidative phosphorylation; transportation into and through cells; glycogen synthesis; glucose utilization, lipogenesis, antiglycogenolysis, antilipolysis, antiprotoelysis, and antigluconeogenesis. All of these functions are altered in diabetes. Insulin acts on many tissues, however, the extent and nature of its action on all tissues is not presently known. There are many similarities of action upon various tissues, but there are also highly significant differences. Some studies have indicated abnormalities in the uptake and action of insulin in some of the peripheral tissue of diabetics. Whether there are defects in the activities of such cells that are of primary importance in the production of diabetes has not been established. Many different hormones significantly influence the net action of insulin, but thus far it is not evident that a disturbance in their activities contributes significantly to the etiology and pathogenesis of genetic diabetes. Insulin is rapidly degraded by essentially all tissues of the body. The mechanism of degradation differs in some tissues, e.g., liver vs. adipose tissue. In vitro studies have demonstrated that chain A and chain B can recombine[long dash]under certain conditions there is a high percentage of recombination. It is also possible for polymers to form, differing significantly in type, size, etc. Consideration is given to the possibility that NSILA constitutes one type of such polymer. It is conceivable that certain polymers would exert insulin-like action and/ or could also inhibit the action of insulin; synalbumin may play such an inhibitory role. Microangiopathies have been observed in a relatively large number of prediabetics. Whether these vascular abnormalities cause significant alterations in carbohydrate metabolism has not been demonstrated.