Potentiators of insulin secretion modulate Ca2+ sensitivity in rat pancreatic islets

Insulin secretion stimulated by 10 mM glucose was potentiated by forskolin, an activator of adenyl cyclase, by acetyl choline which may enhance turnover of inositol phospholipids, and by tetradecanoyl phorbol acetate (TPA), an activator of protein kinase C. None of these agents initiated insulin secretion in the presence of 2 mM glucose. Glucose-stimulated insulin secretion was markedly dependent on the concentration of extracellular Ca2+: at or below 10 microM Ca2+ no insulin secretion was evoked by glucose in freshly isolated islets. The threshold Ca2+ requirement was increased after culture of islets for 44 h. In both fresh and cultured islets the presence of a potentiator of secretion produced both a marked increase in the maximum rate of glucose-stimulated insulin secretion and a lowering of the requirement for extracellular Ca2+. Thus potentiation of insulin release involves an increase in the sensitivity of the B cell to Ca2+.