NICOTINAMIDE PARTIALLY REVERSES THE INTERLEUKIN-1-BETA INHIBITION OF GLUCOSE-INDUCED INSULIN RELEASE IN PANCREATIC-ISLETS

Interleukin-1β (IL-1β) is known to inhibit glucose-induced insulin release by pancreatic islets. We studied the effect of nicotinamide, an inhibitor of poly[adenosine diphosphate (ADP)-ribose] synthetase and a free-radical scavenger, on this IL-1β-induced inhibition using rat pancreatic islets. In static experiments, groups of five islets were incubated for 24 hours in culture medium CMRL-1066, with or without 50 U/mL IL-1β, in the presence or absence of nicotinamide (dose range, 0 to 50 mmol/L), and then exposed for 1 hour to either 1.4 or 19.4 mmol/L glucose, 10 mmol/L arginine, or 10 μmol/L glyburide. Basal insulin secretion was 183 ± 32 pg/islet/h (mean ± SE, n = 7) and 176 ± 39 (n = 7) in control islets and in islets exposed to 50 U/mL IL-1β, respectively. Glucose-stimulated insulin secretion was significantly reduced (185 ± 41) in IL-1β-exposed islets in comparison to control islets (2,037 ± 363). In parallel, arginine-stimulated insulin release was inhibited by IL-1β exposure (166 ± 31 pg/islet/h, mean ± SE, n = 3) in comparison to control islets (1,679 ± 307). In contrast, IL-1β exposure did not significantly reduced glyburide-induced insulin secretion (1,516 ± 231 and 1,236 ± 214 in control and IL-1β-exposed islets, respectively; mean ± SE, n = 3). When islets were simultaneously exposed to IL-1β and increasing concentrations of nicotinamide, a dose-dependent recovery of glucose-induced insulin secretion was observed, with the maximum effect at 25 mmol/L nicotinamide (1,007 ± 123, P < .001). Arginine-stimulated insulin release was also partially restored by the addition of 25 mmol/L nicotinamide. To study the phases of insulin release, groups of 100 islets exposed to IL-1β in the presence or absence of nicotinamide (as in static experiments) were perifused for 20 minutes at 37°C in phosphate buffer with glucose 1.4 mmol/L (basal secretion) and then stimulated with glucose 19.4 mmol/L for 35 minutes. In control islets, glucose-stimulated insulin secretion followed the characteristic biphasic pattern: the first peak was 54.9 ± 9.7 and the second one was 70.8 ± 12.5 pg/islet/min (mean ± SE, n = 7). In islets exposed to IL-1β, both phases were greatly reduced (4.9 ± 1.1 and 7.8 ± 2.2, respectively; P < .001). In the presence of 25 mmol/L nicotinamide, glucose-stimulated insulin secretion was partially restored (19.3 ± 3.9, P < .01 in the first phase, and 28.1 ± 6.7, P < .01 in the second phase). Nicotinamide, therefore, is able to partially prevent the effect of IL-1β on blunting both glucose- and arginine-induced insulin secretion. © 1992.