INTERLEUKIN 1 REDUCES GLYCOLYTIC UTILIZATION OF GLUCOSE BY PANCREATIC ISLETS

大鼠胰岛培养与白细胞介素-1（IL-1）结果 一氧化氮合酶诱导型亚型的上调 （iNOS）和一氧化氮（NO）的过度产生。 这与 可逆性抑制葡萄糖诱导的胰岛素分泌 和胰岛葡萄糖氧化，而这些作用是由 iNOS抑制剂NG-单甲基精氨酸（NMMA）。 IL-1还诱导 非酯化花生四烯酸在胰岛中的积累 NO依赖性机制，如同位素稀释质量所示 光谱法和一个可能解释这种影响， 涉及IL-1诱导的胰岛糖酵解通量的增强。 我们有 因此检测了IL-1对胰岛糖酵解利用的影响， 葡萄糖，并发现在含有IL-1的培养基中培养胰岛 5.5 mM葡萄糖导致胰岛葡萄糖利用的抑制 随后在6至18 mM的葡萄糖浓度下测量。 IL-1诱导的胰岛葡萄糖利用的抑制是 与胰岛葡萄糖激酶mRNA含量下降相关， 通过竞争性RT-PCR测定，并且在葡萄糖激酶蛋白中 合成，如通过免疫沉淀实验所确定的，并且所有 这些影响都被NMMA阻止了。 这些发现表明 IL-1可以下调胰岛葡萄糖激酶，这是主要的 胰岛葡萄糖传感器装置的组成部分，通过NO依赖性 机制 因为已知胰岛葡萄糖激酶水平的降低 导致一种类型的II型糖尿病，这些观察提高 增加胰岛NO水平的因素可能 有助于葡萄糖耐受不良的发展。

Culture of rat pancreatic islets with interleukin-1 (IL-1) results in up-regulation of the inducible isoform of nitric oxide synthase (iNOS) and overproduction of nitric oxide (NO). This is associated with reversible inhibition of both glucose-induced insulin secretion and islet glucose oxidation, and these effects are prevented by the iNOS inhibitor NG-monomethyl-arginine (NMMA). IL-1 also induces accumulation of nonesterified arachidonic acid in islets by an NO-dependent mechanism, as demonstrated by isotope dilution mass spectrometry and one potential explanation for that effect would involve an IL-1-induced enhancement of islet glycolytic flux. We have therefore examined effects of IL-1 on islet glycolytic utilization of glucose and find that culture of islets with IL-1 in medium containing 5.5 mM glucose results in suppression of islet glucose utilization subsequently measured at glucose concentrations between 6 and 18 mM. The IL-1-induced suppression of islet gluc ose utilization is associated with a decline in islet glucokinase mRNA content, as determined by competitive RT-PCR, and in glucokinase protein synthesis, as determined by immuno-precipitation experiments, and all of these effects are prevented by NMMA. These findings suggest that IL-1 can down-regulate islet glucokinase, which is the primary component of the islet glucose-sensor apparatus, by an NO-dependent mechanism. Because reductions in islet glucokinase levels are known to cause a form of type II diabetes mellitus, these observations raise the possibility that factors which increase islet NO levels might contribute to development of glucose intolerance.