Eizirik D L, Leijerstam F
Department of Medical Cell Biology, Uppsala University, Sweden.
Diabete Metab. 1994 Mar-Apr;20(2):116-22.
The enzyme nitric oxide synthase catalyzes the conversion of L-arginine to citrulline and the radical nitric oxide, a short-lived mediator which can be produced in a variety of cell types. Overproduction of nitric oxide is probably implicated in the pathogenesis of several immunologically mediated diseases, including insulin-dependent diabetes mellitus (Type 1). Insulin-producing cells exposed to cytokines, especially interleukin-1, express an inducible form of nitric oxide synthase which is similar to that observed in activated macrophages. Induction of this enzyme mRNA in these cells depends on protein synthesis, and it is probably modulated by protein products of early response genes, such as C-fos. Cytokines seem to activate beta-cell inducible-nitric oxide synthase mostly by stimulating mRNA transcription, but drugs such as nicotinamide and dexamethasone inhibit interleukin 1 induced nitric oxide production by posttranscriptional mechanisms. Considering the potential role for nitric oxide in beta-cell damage during the early stages of Type 1 diabetes, it is of high relevance to further characterize the regulation of this enzyme in insulin-producing cells.
一氧化氮合酶催化L-精氨酸转化为瓜氨酸和自由基一氧化氮，一氧化氮是一种半衰期短的介质，可在多种细胞类型中产生。一氧化氮的过量产生可能与包括胰岛素依赖型糖尿病（1型）在内的几种免疫介导疾病的发病机制有关。暴露于细胞因子，尤其是白细胞介素-1的胰岛素生成细胞表达一种诱导型一氧化氮合酶，其与活化巨噬细胞中观察到的相似。这些细胞中该酶mRNA的诱导依赖于蛋白质合成，并且可能受早期反应基因如C-fos的蛋白质产物调节。细胞因子似乎主要通过刺激mRNA转录来激活β细胞诱导型一氧化氮合酶，但烟酰胺和地塞米松等药物通过转录后机制抑制白细胞介素1诱导的一氧化氮产生。考虑到一氧化氮在1型糖尿病早期β细胞损伤中的潜在作用，进一步表征该酶在胰岛素生成细胞中的调节具有高度相关性。
