Regulation of proinsulin synthesis in isolated rat islets.

(1) A system is described for studying the short-term effects of agents on proinsulin synthesis in vitro, as measured by the incorporation of [3H]leucine into isolated proinsulin. (2) Of the agents tested, glucose has the most marked, and apparently earliest, effect on proinsulin synthesis. (3) The adenyl cyclase system participates in the regulation of proinsulin synthesis since exogenous cyclic AMP, glucagon, and caffeine are stimulatory. When cyclic AMP is added to the medium in the presence of glucose, it is the most potent agent acting on the adenyl cyclase-phosphodiesterase system. (4) The addition of NADPH to isolated rat islets inhibits proinsulin and Bulk Protein synthesis in vitro.