Nitric oxide produced by inducible nitric oxide synthase in islets exerts inhibitory and cytotoxic effects on pancreatic β cells and is therefore thought to be a potent mediator in the pathogenesis of Type I diabetes mellitus. Here, using isolated rat pancreatic islets, we show that high-concentration nicotinamide (20 mM), but not low-concentration nicotinamide (5 mM) attenuates the interleukin-1β-evoked inhibition of glucose-induced insulin secretion by preventing the induction of interferon regulatory factor-1, a transcriptional factor which plays an essential role in inducible nitric oxide synthase gene expression, and the interleukin-1β-induced nitric oxide formation. High-concentration nicotinamide also restored an interleukin-1β-induced decrease in ATP content in pancreatic β cells, suggesting that interleukin-1β-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.
|Number of pages||7|
|Journal||Biochemical and biophysical research communications|
|Publication status||Published - 1995 Jan 1|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology