Short-term exposure to glucose increases insulin secretion during subsequent stimulation. We investigated the effect of the new regulatory peptide pancreastatin on this priming effect of glucose in the perfused rat pancreas. Pancreastatin (33-49) at a concentration of 10(-8) M inhibited insulin release when stimulated by glucose at a concentration of 16.7 mM. However, after a second pulse of 16.7 mM glucose, pancreastatin potentiated the priming effect of glucose on insulin secretion. The modulation of insulin secretion by pancreastatin results in a potentiation of the priming effect of glucose in the rat pancreas, suggesting a role for pancreastatin in the adaptation of the B cell to glucose-stimulated insulin secretion.