TY - JOUR
T1 - Nicotinamide Inhibits IRF-1 mRNA Induction and Prevents IL-1β-Induced Nitric Oxide Synthase Expression in Pancreatic β Cells
AU - Akabane, Atsuya
AU - Kato, Ichiro
AU - Takasawa, Shin
AU - Unno, Michiaki
AU - Yonekura, Hideto
AU - Yoshimoto, Takashi
AU - Okamoto, Hiroshi
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1995.2496
DO - 10.1006/bbrc.1995.2496
M3 - Article
C2 - 7487987
AN - SCOPUS:0028861996
VL - 215
SP - 524
EP - 530
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -