Evidence That Insulin Release Is the Mechanism for Experimentally Induced Leucine Hypoglycemia in Man.

In a previous report (1), we have described studies dealing with the experimental induction in man of sensitivity to leucine hypoglycemia. In healthy subjects, marked sensitivity to leucine hypoglycemia was consistently induced by prior administration of sulfonylureas, compounds that are known to stimulate islet-cell activity. On the other hand, after pretreatment with Novo Ultralente insulin, administration of leucine produced decreases in blood glucose levels that, although significant, were small and inconsistent. A modest but significant hypoglycemic effect was also produced in some healthy subjects by administering leucine without prior administration of hypoglycemic agents ( 1, 2). The magnitude of these decreases in blood glucose levels was similar to that observed after administration of leucine to subjects pretreated with Ultralente insulin. From the results of these studies, we concluded that in man release of additional insulin is the primary mechanism by which leucine decreases the blood sugar in experimentally induced sensitivity to leucine hypoglycemia. Earlier reports had demonstrated an increase in concentration of plasma insulin during leucine-induced hypoglycemia, both in infants with idiopathic hypoglycemia (3-5) and in patients with islet-cell tumors (1, 6-8). The present study, employing an immunoassay for insulin, was undertaken to determine the relationship between endogenous insulin and the induction of experimentally induced leucine hypo-