Calcium deprivation enhances glucagon release in the presence of 2-ketoisocaproate.

The effect of calcium deprivation upon glucagon and insulin release was studied in the rat pancreas perfused in the presence of 2-ketoisocaproate (10 mM). Control perfusions were conducted in the presence of glucose (11.1 mM). In the presence of 2-ketoisocaproate, the decrease in the extracellular concentration of calcium provoked a dramatic, but reversible, enhancement of glucagon release. Such a secretory response was similar in pattern to that seen upon calcium omission in the presence of glucose. Bio-Gel P-30 chromatographic studies showed that only true glucagon (mol wt, 3500) was liberated in the pancreatic effluent during the period of calcium deprivation. On the other hand, the secretion of insulin induced by 2-ketoisocaproate was, like that elicited by glucose, markedly inhibited upon the decrease in extracellular calcium concentration (80% and 65% inhibition, respectively). The results are interpreted in support of the hypothesis that calcium may play an inhibitory role in the control of glucagon release. It is suggested that such a role is somehow linked to the metabolism of exogenous nutrients in the A2 cells.