Nicotinamide, a poly (ADP-ribose) synthetase inhibitor, ameliorates B-cell function in partially depancreatized rats

We studied the effect of nicotinamide, a poly (ADP-ribose) synthetase inhibitor, on B-cell functions in 7-week-old male Wistar rats after 90% pancreatectomy (Px). Nicotinamide (0.5 g/kg body wt.) was injected once a day i.p. from 1 week before the surgery, and the injection was continued for 12 weeks after Px. Plasma glucose levels were significantly lower in Px rats treated with nicotinamide (NA rats) than in Px rats without treatment. In in vitro experiments with perfusion of the isolated pancreas, insulin secretion induced by 16.7 mM glucose was blunted in Px rats whereas insulin secretion induced by 19 mM arginine was increased. Nicotinamide treatment restored glucose-induced insulin secretion to normal and partly suppressed the hyperresponse of insulin to arginine. In addition, nicotinamide partially restored the priming effect induced by 28 mM glucose. The insulin content of the perfused pancreas was slightly but significantly greater in NA rats than in Px rats. Histological examination revealed fibrotic degeneration and degranulation in the islets of Px rats, whereas the normal structure was retained in most islets of NA rats. These results suggest that nicotinamide ameliorates islet function in partially depancreatized rats.