Eizirik D L, Sandler S, Welsh N, Bendtzen K, Hellerström C
Department of Medical Cell Biology, Uppsala University, Sweden.
Autoimmunity. 1994;19(3):193-8. doi: 10.3109/08916939408995694.
It has been recently reported that human pancreatic islets in tissue culture produce nitric oxide (NO) and show a decreased function when exposed for 6 days to combinations of cytokines (interleukin-1 beta (IL-1 beta) + tumor necrosis factor-alpha (TNF-alpha) + interferon-gamma (IFN-gamma). Here we study the effects of nicotinamide (Nic; 10 or 20 mmol/l) on these deleterious effects of cytokines (50 U/ml IL-1 beta + 1000 U/ml TNF-alpha + 1000 U/ml IFN-gamma). Islets were isolated from 8 human pancreata at the Central Unit of the beta-Cell Transplant, Brussels, sent to Uppsala and, after 3-5 days in culture, exposed for 6 additional days to the cytokines and/or Nic. The cytokines induced a 6-fold increase in islet NO production (P < 0.001), and this effect was partially counteracted by Nic (50-60% decrease in NO production; P < 0.001). The cytokines severely decreased the islet insulin content and glucose-induced insulin release (16.7 mmol/l glucose; 90% decrease; P < 0.001). Both these effects of cytokines were partially counteracted by Nic, especially at the highest concentration (20 mmol/l; 2-4-fold increase compared to islets exposed to cytokines alone; P < 0.01). Nic by itself did not affect the insulin content or insulin release by control islets. In conclusion, the present data indicate that Nic counteracts the deleterious effects of cytokines on human pancreatic islets. This effect of Nic may be relevant for the beneficial effects of the drug in early IDDM.
最近有报道称，组织培养中的人胰岛会产生一氧化氮（NO），并且当暴露于细胞因子组合（白细胞介素-1β（IL-1β）+肿瘤坏死因子-α（TNF-α）+干扰素-γ（IFN-γ））6天时，其功能会降低。在此，我们研究烟酰胺（Nic；10或20 mmol/l）对细胞因子（50 U/ml IL-1β + 1000 U/ml TNF-α + 1000 U/ml IFN-γ）这些有害作用的影响。胰岛从布鲁塞尔β细胞移植中心单元的8个人类胰腺中分离出来，送到乌普萨拉，在培养3 - 5天后，再额外暴露于细胞因子和/或Nic 6天。细胞因子使胰岛NO产生增加了6倍（P < 0.001），而这种作用被Nic部分抵消（NO产生减少50 - 60%；P < 0.001）。细胞因子严重降低了胰岛胰岛素含量和葡萄糖诱导的胰岛素释放（16.7 mmol/l葡萄糖；降低90%；P < 0.001）。细胞因子的这两种作用都被Nic部分抵消，尤其是在最高浓度时（20 mmol/l；与仅暴露于细胞因子的胰岛相比增加2 - 4倍；P < 0.01）。Nic本身对对照胰岛的胰岛素含量或胰岛素释放没有影响。总之，目前的数据表明Nic可抵消细胞因子对人胰岛的有害作用。Nic的这种作用可能与该药物在早期胰岛素依赖型糖尿病中的有益作用相关。
