title: Nicotinamide inhibits IRF-1 mRNA induction and prevents IL-1 beta-induced nitric oxide synthase expression in pancreatic beta cells.
abstract: Nitric oxide produced by inducible nitric oxide synthase in islets exerts inhibitory and cytotoxic effects on pancreatic beta 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-1 beta-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-1 beta-induced nitric oxide formation. High-concentration nicotinamide also restored an interleukin-1 beta-induced decrease in ATP content in pancreatic beta cells, suggesting that interleukin-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.
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D001549:Benzamides / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D050856:Interferon Regulatory Factor-1; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009536:Niacinamide / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis*; D019323:omega-N-Methylarginine
chemical_list: D001549:Benzamides; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D007375:Interleukin-1; C494258:Irf1 protein, mouse; C494259:Irf1 protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C025160:3-aminobenzamide; D000255:Adenosine Triphosphate; D001120:Arginine; D019001:Nitric Oxide Synthase; D005947:Glucose