L-Leucine-Induced Secretion of Glucagon and Insulin, and the “Off-Response” to L-Leucine in Vitro. II. The Role of D-Glucose*

Abstract

The role of glucose in L-[LEU]-induced secretion of glucagon and insulin was investigated in the isolated, perfused rat pancreas. In the absence of glucose (or with 2.8 mM D-glucose) in the perfusion medium, the observed augmentation of the acute phase release of glucagon diminished gradually upon repetitive perfusions of L-Leu. A late phase release was not observed with Leu concentrations up to 10 mM L-Leu evoked acute phase release of insulin at concentrations of 5 and 10 mM, but not 2 mM. The release of insulin which was obsserved shortly after the termination of the perfusion of -Leu (off-response) in the presence of 5.6 mM D-glucose failed to occur. In the presence of 16.7 mM D-glucose, acute phase glucagon release was blunted, but there was a marked late phase release with 10 mM L-Leu. L-Leu evoked insulin evoked insulin release with 10 mM L-Leu of 2 mM. The insulin off-response occurred. With 10 mM D-mannoheptulose plus 5.6 mM D-glucose, a small glucagon off-response occurred upon removal of L-leucine; the acute or late phases of Leu-induced insulin release or the insulin off-response failed to occur. With 5.6 mM 3-o-D-methylglucose, the insulin off-response to -Leu occurred in the presence but not in the absence of glucose. With 5 mM fumarate, glutamate and pyruvate, but without glucose, during L-Leu perfusion, the acute phase of glucagon release occurred and the late phase was inhibited; the insulin off-response failed to occur. The magnifying effect of glucose deprivation on the secretion of glucagon was evanescent. With an abundance of glucose, the integrity of the mechamisms of synthesis and release of glucagon may be preserved better than in the absence of glucose. Glucose plays a permissive role in -LEU-induced insulin release and in the insulin off-response to -Leu. The metabolism of glucose seems to be essential for the insulin off-response to L-Leu to occur.