Cytokines, in particular IL-1, released mainly by infiltrating macrophages, can be one of the key mediators of immune-induced beta-cell destruction in IDDM. IL-1 is able to induce suppression of insulin release and biosynthesis in cultured rat pancreatic islets. In addition, the cytokine shows clear cytotoxic effects leading to beta-cell death. The proposed mechanisms of action of IL-1 after binding to the beta-cell receptors are varied. Concerning the cytotoxic effects of the cytokine, the role of oxygen free radicals, mainly derived from arachidonate metabolism (see Fig. 1) is clear, and possibly potentiated by a cytosolic Na(+)-mediated alkalinization of the beta-cell exposed to the cytokine. In fact, an increased influx of Na+ may explain some of the cytotoxicity since it results in concomitant water uptake leading to swelling of the endoplasmic reticulum. NO formation also seems to be related to the cytokine-induced cytotoxicity since inhibition of the NO synthase abolishes the effects of the cytokine (see Fig. 1). In relation to the inhibitory effects of the cytokine on the beta-cell, different studies point toward almost all known second messenger systems already described for several hormones, such as cAMP formation, increased phospholipase C activity, changes in cytosolic Ca++, and altered gene transcription (see Fig. 1). Of particular interest is the protease activation associated with IL-1 (a serine protease) that seems to be clearly connected with the effects of the cytokine upon the beta-cell. In conclusion, the different studies devoted to the problem of IL-1 signal transduction on the beta-cell seem to indicate that the action of the cytokine on the pancreatic insulin-secreting cells is not associated with an individual second messenger system but rather seems to be related to a plurifactorial transduction system.

中文翻译：

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白介素-1和β细胞功能：超过一秒钟的信使？

主要通过浸润巨噬细胞释放的细胞因子，特别是IL-1，可能是IDDM中免疫诱导的β细胞破坏的关键介质之一。IL-1能够在培养的大鼠胰岛中诱导胰岛素释放的抑制和生物合成。此外，细胞因子显示出明显的细胞毒性作用，导致β细胞死亡。所提出的与β细胞受体结合后IL-1的作用机制是变化的。关于细胞因子的细胞毒性作用，主要来自花生四烯酸代谢的氧自由基的作用是清楚的（见图1），并且可能通过暴露于β-内酰胺酶的β-细胞的细胞溶质Na（+）介导的碱化作用而增强。细胞因子。事实上，Na +流入量的增加可能会解释某些细胞毒性，因为它会导致水的吸收，从而导致内质网膨胀。由于抑制NO合酶消除了细胞因子的作用，NO的形成似乎也与细胞因子诱导的细胞毒性有关（见图1）。关于细胞因子对β细胞的抑制作用，不同的研究指向几乎已经描述的几种激素的所有已知第二信使系统，例如cAMP的形成，磷脂酶C活性的增加，胞质Ca ++的改变以及基因转录的改变。 （见图1）。特别令人感兴趣的是与IL-1（丝氨酸蛋白酶）有关的蛋白酶活化作用，似乎与细胞因子对β细胞的作用明显相关。结论，