Tsuura Y, Ishida H, Shinomura T, Nishimura M, Seino Y
Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Kyoto, Japan.
Biochem Biophys Res Commun. 1998 Nov 9;252(1):34-8. doi: 10.1006/bbrc.1998.9601.
The physiological role of nitric oxide (NO) on the mechanism of insulin secretion is unknown, but some studies suggest that NO affects glucose metabolism in pancreatic beta-cells. We have aimed at clarifying the physiological role of endogenous NO and its target in the glucose metabolism of beta-cells. The expression of brain-type NO synthase (bNOS) was detected in pancreatic islets by Western blotting. Under the condition of elevated intracellular Ca2+ concentration induced in the beta-cells by high glucose and forced depolarization by 40 mM K+, the generation of NO from the islets was enhanced. This increase was suppressed by the NOS blockers, N-iminoethyl-l-ornithine (L-NIO), and exposure to Ca2+-free extracellular solution. In addition, the NOS blockers L-NIO and 7-nitro indazole (7-NI) enhanced glucose-induced but not glyceraldehyde- or KIC-induced insulin secretion. In an in vitro enzyme study, the NO donor sodium nitroprusside (SNP) suppressed phosphofructokinase activity and activated glucokinase and glucose-6-phosphate isomerase activity, but SNP significantly inhibited the combined activity of the enzymes. This suggests that endogenous NO has an inhibitory role on insulin release induced by glucose and that its underlying mechanism is the suppression of phosphofructokinase activity in glycolysis.
一氧化氮（NO）在胰岛素分泌机制中的生理作用尚不清楚，但一些研究表明，NO会影响胰腺β细胞中的葡萄糖代谢。我们旨在阐明内源性NO及其在β细胞葡萄糖代谢中的作用靶点的生理作用。通过蛋白质免疫印迹法在胰岛中检测到脑型一氧化氮合酶（bNOS）的表达。在高葡萄糖诱导β细胞内Ca2+浓度升高以及40 mM K+强制去极化的条件下，胰岛中NO的生成增强。这种增加被一氧化氮合酶抑制剂N-亚氨基乙基-L-鸟氨酸（L-NIO）以及暴露于无Ca2+的细胞外溶液所抑制。此外，一氧化氮合酶抑制剂L-NIO和7-硝基吲唑（7-NI）增强了葡萄糖诱导的胰岛素分泌，但未增强甘油醛或α-酮异己酸诱导的胰岛素分泌。在一项体外酶研究中，NO供体硝普钠（SNP）抑制了磷酸果糖激酶的活性，并激活了葡萄糖激酶和葡萄糖-6-磷酸异构酶的活性，但SNP显著抑制了这些酶的联合活性。这表明内源性NO对葡萄糖诱导的胰岛素释放具有抑制作用，其潜在机制是抑制糖酵解中磷酸果糖激酶的活性。
