Summary
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 °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. These findings suggest that nicotinamide protected the islet B-cells against killing by SZ probably through an inhibition of the enzyme poly(ADP-ribose) synthetase, but not against a long-lasting injury affecting the mechanisms involved in the islet glucose-stimulated insulin secretion. This latter injury may be due to a deficient energy generation in the islet B-cells, probably related to an impaired mitochondrial function.
Key Words
Culture - Insulin release - Nicotinamide - Pancreatic islets - Poly(ADP-ribose)synthetase - Streptozotocin
