Phentolamine reverses NPY-induced inhibition of insulin secretion in isolated rat islets.

It has been shown that the rodent pancreas is innervated by neuropeptide Y (NPY) nerves, some of which are adrenergic, and that NPY inhibits glucose-induced insulin secretion in vivo in the mouse and that from isolated rat islets in vitro. We now investigated whether the alpha-adrenoceptor antagonist phentolamine affects the inhibitory action of NPY on insulin secretion from isolated rat islets. It was found that NPY dose dependently inhibited insulin secretion stimulated by glucose (11.1 mM). At a concentration of 10(-7) M, NPY totally abolished the insulin secretory response to glucose. It was also found that incubation with the alpha-adrenoceptor antagonist phentolamine (10(-6) M) itself enhanced the insulin secretion at 3.3 mM but not at 16.7 mM glucose. Moreover, phentolamine counteracted the inhibitory action of NPY. Thus, at 10(-8) M, NPY could no longer inhibit insulin secretion when phentolamine (10(-6) M) was present, whether 3.3 mM or 11.1 mM glucose was present. In contrast, somatostatin (10(-7) M) could inhibit insulin secretion, both in the presence and absence of phentolamine (10(-6) M); this showed that phentolamine does not reverse all types of inhibition. However, when the dose of phentolamine was decreased to 10(-7) M, the inhibitory action of NPY on glucose-induced insulin secretion was retained indicating that the reversal of the NPY effect by phentolamine is a competitive effect. It is concluded that NPY inhibits glucose-induced insulin secretion by a direct action on the islets, and that phentolamine reverses this inhibitory action of NPY in a competitive manner.