Pipeleers D, Hoorens A, Marichal-Pipeleers M, Van de Casteele M, Bouwens L, Ling Z
Diabetes Research Center, Vrije Universiteit Brussel, Belgium.
Diabetes. 2001 Feb;50 Suppl 1:S52-7. doi: 10.2337/diabetes.50.2007.s52.
Studies on the pathogenesis of type 1 diabetes have mainly focused on the role of the immune system in the destruction of pancreatic beta-cells. Lack of data on the cellular and molecular events at the beta-cell level is caused by the inaccessibility of these cells during development of the disease. Indirect information has been collected from isolated rodent and human islet cell preparations that were exposed to cytotoxic conditions. This article reviews in vitro experiments that investigated the role of beta-cells in the process of beta-cell death. beta-Cells rapidly die in necrosis because of toxic levels of oxidizing radicals or of nitric oxide; they progressively become apoptotic after prolonged culture at low glucose or with proinflammatory cytokines. Their susceptibility to necrosis or apoptosis varies with their functional state and thus with the environmental conditions. A change in cellular phenotype can alter its recognition of potentially cytotoxic agents and its defense mechanisms against cell death. These observations support the view that beta-cells are not necessarily passive victims of a cytotoxic process but can actively participate in a process of beta-cell death. Their role will be influenced by neighboring non-beta-cells, which can make the islet internal milieu more protective or toxic for the beta-cells. We consider duct cells as potentially important contributors to this local process.
1型糖尿病发病机制的研究主要集中在免疫系统在胰腺β细胞破坏中的作用。在疾病发展过程中，由于这些细胞难以获取，因此缺乏关于β细胞水平细胞和分子事件的数据。间接信息是从暴露于细胞毒性条件下的分离的啮齿动物和人类胰岛细胞制剂中收集的。本文综述了研究β细胞在β细胞死亡过程中作用的体外实验。由于氧化自由基或一氧化氮的毒性水平，β细胞会迅速坏死；在低葡萄糖或促炎细胞因子存在下长时间培养后，它们会逐渐发生凋亡。它们对坏死或凋亡的易感性因其功能状态而异，因此也因环境条件而异。细胞表型的改变会改变其对潜在细胞毒性剂的识别及其对细胞死亡的防御机制。这些观察结果支持这样一种观点，即β细胞不一定是细胞毒性过程的被动受害者，而是可以积极参与β细胞死亡过程。它们的作用将受到邻近非β细胞的影响，这些非β细胞可以使胰岛内部环境对β细胞更具保护作用或毒性。我们认为导管细胞是这一局部过程的潜在重要贡献者。
