Relationships Between Arginine and Glucose in the Induction of Insulin Secretion from the Isolated, Perfused Rat Pancreas1

In an attempt to detect differences in insulin secretion induced by glucose and arginine and to observe their interaction, we studied responses in the isolated rat pancreas. We found that: Insulin was secreted in the absence of glucose, with arginine concentrations as low as 60 mg/100 ml, and was characterized by gradual increase to a plateau. Prolonged infusions of arginine without glucose produced a waning effect which was reduced with the addition of glucose; Arginine superimposed upon glucose (50, 70, 100, and ISO mg/100 ml) responded multiphasically, i.e., an early (spike) discharge, a fall, and subsequently a late rise pattern of insulin secretion. At high levels of glucose (300 and 500 mg/100 ml) arginine did not significantly alter the secretory pattern induced by the glucose; After arginine was withdrawn from systems containing high concentrations of glucose (150, 300, and 500 mg/100 ml), insulin secretion appeared transiently less than would be expected for these high glucose levels; Arginine decreased the ability of subsequent high levels of glucose to elicit an early discharge of insulin. These data imply that there is a difference in the mechanism of action of glucose and arginine, and that arginine has both positive and negative interactions with glucose. It is suggested that arginine, in the presence or absence of glucose, empties the labile insulin compartment but does not provide substrates, or insulin, or both. This is in contrast to glucose which has been characterized by emptying of the labile compartment and provision to that compartment. (Endocrinology90: 624, 1972)