Horton R A, Knowles R G, Titheradge M A
School of Biological Sciences, University of Sussex, Brighton, U.K.
Biochem Biophys Res Commun. 1994 Oct 28;204(2):659-65. doi: 10.1006/bbrc.1994.2510.
Treatment of rats with bacterial endotoxin resulted in a significant induction of hepatic nitric oxide synthase within 3 hours. The response was maximal at 12 hours and was maintained over 18 hours. The induction of nitric oxide synthase correlated well with the increase in plasma nitrate plus nitrite concentrations and also with the inhibition of glucose synthesis in subsequently isolated hepatocytes. The decline in the rate of gluconeogenesis also correlated with an inhibition of flux through phosphoenolpyruvate carboxykinase but not with alterations in flux through either pyruvate kinase or 6-phosphofructo-1-kinase, suggesting that a nitric oxide-induced inhibition of phosphoenolpyruvate carboxykinase may underlie the decreased glucose production in sepsis.
用细菌内毒素处理大鼠，在3小时内可显著诱导肝脏一氧化氮合酶。该反应在12小时时达到最大值，并持续18小时以上。一氧化氮合酶的诱导与血浆硝酸盐加亚硝酸盐浓度的增加以及随后分离的肝细胞中葡萄糖合成的抑制密切相关。糖异生速率的下降也与磷酸烯醇式丙酮酸羧激酶通量的抑制相关，但与丙酮酸激酶或6-磷酸果糖-1-激酶通量的改变无关，这表明一氧化氮诱导的磷酸烯醇式丙酮酸羧激酶抑制可能是脓毒症中葡萄糖生成减少的基础。
