Time-course of Ca2+-induced insulin secretion from perifused, electrically permeabilised islets of Langerhans: effects of cAMP and a phorbol ester.

The pattern of insulin secretion from electrically permeabilised islets was studied in a perifusion system. Increases in intracellular Ca2+ stimulated insulin secretion in a dose-related manner, but the secretory response to Ca2+ was only transient, with permeabilised islets becoming rapidly insensitive to a stimulatory concentration of Ca2+. Cyclic AMP and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), both stimulated Ca2+-induced insulin secretion from perifused permeabilised islets by increasing the maximum secretory response to Ca2+, and by maintaining elevated rates of secretion when the permeabilised islets had become insensitive to the stimulatory effects of Ca2+. These results suggest that cAMP and PMA may act partly by modifying the magnitude of the secretory response to Ca2+, and also by Ca2+-independent effects on the secretory mechanism.