Akabane A, Kato I, Takasawa S, Unno M, Yonekura H, Yoshimoto T, Okamoto H
Department of Biochemistry, Tohoku University School of Medicine, Miyagi, Japan.
Biochem Biophys Res Commun. 1995 Oct 13;215(2):524-30. doi: 10.1006/bbrc.1995.2496.
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.
胰岛中诱导型一氧化氮合酶产生的一氧化氮对胰腺β细胞具有抑制和细胞毒性作用，因此被认为是I型糖尿病发病机制中的一种强效介质。在此，我们使用分离的大鼠胰岛表明，高浓度烟酰胺（20 mM）而非低浓度烟酰胺（5 mM）可通过阻止干扰素调节因子-1的诱导来减轻白细胞介素-1β引起的对葡萄糖诱导的胰岛素分泌的抑制作用，干扰素调节因子-1是一种转录因子，在诱导型一氧化氮合酶基因表达中起重要作用，同时高浓度烟酰胺还可抑制白细胞介素-1β诱导的一氧化氮形成。高浓度烟酰胺还恢复了白细胞介素-1β诱导的胰腺β细胞中ATP含量的降低，这表明白细胞介素-1β诱导的一氧化氮抑制了线粒体功能。目前的结果显示了高剂量烟酰胺对I型糖尿病预防作用的分子基础。
