Pancreastatin inhibits insulin secretion from isolated rat islets: studies on its mechanism of action.

The peptide pancreastatin is known to inhibit insulin secretion. To study its mechanism of action, we examined the effects of pancreastatin on 45Ca(2+)- and 86Rb(+)-efflux from isolated rat islets. We found that glucose (8.3 mmol/l)-stimulated insulin secretion was totally abolished by pancreastatin (100 nmol/l). It is known that glucose reduces the 86Rb(+)-efflux and increases the 45Ca(2+)-efflux from prelabelled islets, which reflects its action on the K(+)- and Ca(2+)-permeabilities. We found that pancreastatin reduced the glucose-stimulated increase in 45Ca(2+)-efflux without affecting the 86Rb(+)-efflux. This shows that pancreastatin inhibits the action of glucose on Ca(2+)-channels, without influencing the closure of K(+)-channels induced by the sugar. The results indicate that pancreastatin does not inhibit insulin secretion by hyperpolarizing the B-cells, but rather that the peptide inhibits insulin secretion by inhibiting the glucose-stimulated B-cell Ca(2+)-uptake that evolves by depolarization.