The Experimental Induction in Man of Sensitivity to Leucine Hypoglycemia*

Woolf (1) reported that oral administration of L-leucine induces a sharp fall in blood glucose levels in some children with idiopathic familial hypoglycemia, but that it has no effect in normal subjects. Flanagan, Schwartz, and Ryan (2) were the first to report that oral administration of L-leucine to patients with functioning islet-cell tu-mors also produces a hypoglycemic effect. By the immunoassay of Yalow and Berson for meas-urement of plasma insulin, an increase has been demonstrated in concentration of plasma insulin during leucine-induced hypoglycemia in infants with idiopathic hypoglycemia (3-5) and in pa-tients with islet-cell tumors (3, 6, 7). The studies described below had the following objectives: 1) to see if healthy people could be made sensitive to the hypoglycemic action of leucine, and 2) to study the mechanism by which leucine causes hypoglycemia. The results of this study indicate 1) that sensitivity to leucine hypo-glycemia can be induced consistently in healthy subjects after the oral administration of sulfonyl-urea compounds, and 2) that release of additional insulin is the primary mechanism of action by which leucine causes hypoglycemia in man.' METHODS Leucine tests were performed after an overnight fast 1) by the oral administration of 0.2 g per kg of an