Survival and B-Cell Function of Mouse Pancreatic Islets Maintained in Culture after Concomitant Exposure to Streptozotocin and Nicotinamide

Abstract

It has recently been suggested from experiments performed on isolated pancreatic islets in vitro, that streptozotocin (SZ) may exert a progressive damage to the islet B-cells. It may be that this damaging effect is not dependent on the acute activation of the enzyme poly(ADP-ribose) synthetase, and a subsequent depletion of the islet NAD content. In the present study we have exposed mouse pancreatic islets in vitro to 2.2 mM SZ for 30 min at 37 degrees C, in the presence or absence of 10 mM nicotinamide, an inhibitor of poly(ADP-ribose) synthetase and examined the islet function immediately (Day 0) or after six days of culture (Day 6). Nicotinamide protected the islets against an inhibition of the glucose-stimulated insulin release on day 0 and against a SZ-induced loss in islet number and islet insulin content on day 6. However, on day 6 the islets incubated with SZ in the presence of nicotinamide showed an inhibition of the insulin release comparable to that observed in islets treated with SZ in the absence of nicotinamide. Furthermore, on day 0 nicotinamide counteracted a SZ-induced impairment of islet glucose oxidation, whereas on day 6 islets incubated with SZ both in the absence or presence of nicotinamide showed a similar and more markedly impaired oxidation of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)