A. Akabane et al., NICOTINAMIDE INHIBITS IRF-1 MESSENGER-RNA INDUCTION AND PREVENTS IL-1-BETA-INDUCED NITRIC-OXIDE SYNTHASE EXPRESSION IN PANCREATIC BETA-CELLS, Biochemical and biophysical research communications, 215(2), 1995, pp. 524-530
Nitric oxide produced by inducible nitric oxide synthase in islets exe
rts inhibitory and cytotoxic effects on pancreatic beta cells and is t
herefore thought to be a potent mediator in the pathogenesis of Type I
diabetes mellitus. Here, using isolated rat pancreatic islets, we sho
w that high-concentration nicotinamide (20 mM), but not low-concentrat
ion nicotinamide (5 mM) attenuates the interleukin-1 beta-evoked inhib
ition of glucose-induced insulin secretion by preventing the induction
of interferon regulatory factor-1, a transcriptional factor which pla
ys an essential role in inducible nitric oxide synthase gene expressio
n, and the interleukin-1 beta-induced nitric oxide formation. High-con
centration nicotinamide also restored an interleukin-1 beta-induced de
crease in ATP content in pancreatic beta cells, suggesting that interl
eukin-1 beta-induced nitric oxide inhibits the mitochondrial function.
The present results show the molecular basis of the preventive effect
of high-dose nicotinamide on type I diabetes mellitus. (C) 1995 Acade
mic Press, Inc.