Role of second messengers in the regulation of glucagon secretion from isolated rat islets of Langerhans.

The roles of diacylglycerol (DAG), cAMP and Ca2+ in mediating the stimulatory action of arginine on pancreatic A cells have been investigated using phorbol esters, forskolin, a Ca2+ ionophore and trifluoroperazine (TFP). 0.5 microM 4 beta-phorbol 12-myristate 13-acetate (PMA) which stimulated glucagon secretion by approximately 3-fold in the absence of arginine, was unable to enhance arginine-stimulated glucagon secretion. Higher concentrations (1 and 10 microM) of PMA were able to enhance glucagon secretion in the presence of 1.25, 2.5, 5 but not 10 mM arginine. Insulin secretion was enhanced by PMA under all the conditions tested. Arginine (10 and 20 mM)-stimulated secretion of glucagon and insulin were synergistically augmented by 20 microM forskolin. While the effects of forskolin plus PMA on the A cells were additive, the effects of the two agents on the B cells were synergistic. The responses of the A and B cells to arginine required extracellular Ca2+. Secretion of the two hormones was dose-dependently stimulated by A23187. Arginine-stimulated glucagon secretion but not insulin secretion, was dose-dependently inhibited by TFP. These results suggest that proposed cellular second messengers interact differently in the A and B cells, and DAG and Ca2+ may play pivotal roles in mediating the actions of arginine on the A but not B cells; cAMP may play a modulatory role in the A cell response to arginine.