Nicotinamide partially reverses the interleukin-1 beta inhibition of glucose-induced insulin release in pancreatic islets.
Interleukin-1 beta (IL-1 beta) 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-1 beta-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-1 beta, 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 mumols/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-1 beta, respectively. Glucose-stimulated insulin secretion was significantly reduced (185 +/- 41) in IL-1 beta-exposed islets in comparison to control islets (2,037 +/- 363). In parallel, arginine-stimulated insulin release was inhibited by IL-1 beta exposure (166 +/- 31 pg/islet/h, mean +/- SE, n = 3) in comparison to control islets (1,679 +/- 307). In contrast, IL-1 beta exposure did not significantly reduce glyburide-induced insulin secretion (1,516 +/- 231 and 1,236 +/- 214 in control and IL-1 beta-exposed islets, respectively; mean +/- SE, n = 3). When islets were simultaneously exposed to IL-1 beta 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 less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Buscema
M
M
Department of Endocrinology, University of Catania, Italy.
Vinci
C
C
Gatta
C
C
Rabuazzo
M A
MA
Vignen
R
R
Purrello
F
F
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009536:Niacinamide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D009536:Niacinamide; D005947:Glucose