L-Leucine-Induced Secretion of Glucagon and Insulin, and the “Off-Response” to L-Leucine in Vitro. I. Characterization of the Dynamics of Secretion*

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Abstract
The effects of L-Leu, D-Leu and L-Ile upon the secretion of glucagon and insulin were investigated using the isolated, perfused rat pancreas. All experiments were conducted in the presence of 5.6 mM D-glucose. Ten minute perfusions of 2, 5 and 10 mM L-Leu induced the release of glucagon and insulin in a dose-related manner. The removal of L-Leu was followed by renewed release of insulin (off-response) but not of glucagon. The magnitude of the off-response was greater when L-Leu was perfused over longer periods. L-Ile evoked the release of both glucagon and insulin. When L-Leu was administered during perfusion of L-Ile, L-Leu-induced release of glucagon was inhibited, that of insulin was augmented, and the insulin off-response prevailed. When the perfusion of L-Leu immediately preceded that of L-Ile, L-Ile-induced release of glucagon was abolished and that of insulin was augmented. D-Leu evoked the release of glucagon but not of insulin, and no off-response occurred. When the perfusion of D-Leu followed that of L-Leu, D-Leu-induced glucagon release was inhibited; the insulin off-response to L-Leu was not altered. Glucagon release induced by L-Leu, D-Leu, or L-Ile may be related to the occupancy by these analogous amino acids of transport and/or receptor sites which they share. The insulin off response to L-Leu may be evoked by events which take place during the period of administration of L-Leu; these events are not likely to be the release of insulin that occurs during perfusion of L-Leu or the transport of L-Leu into or out of the .beta. cell. Structurally or chemically similar compounds which are secretagogues both for glucagon and insulin affect the release of these hormones in different ways; these differences are likely to be due to dissimilar mechanisms governing the secretion of the 2 hormones.