Type 1 diabetes mellitus (T1DM) is caused by pancreatic β-cell dysfunction and apoptosis, with consequent severe insulin deficiency. Thus, β-cell protection may be a primary target in the treatment of T1DM. Evidence has demonstrated that defective mitochondrial function plays an important role in pancreatic β-cell dysfunction and apoptosis; however, the fundamental effect of mitochondrial complex I action on β-cells and T1DM remains unclear. In the current study, the pancreas protective effect of complex I inhibitor rotenone (ROT) and its potential mechanism were assessed in a streptozotocin (STZ)-induced mouse model of T1DM and in cultured mouse pancreatic β-cell line, Min6. ROT treatment exerted a hypoglycemic effect, restored the insulin level, and decreased inflammation and cell apoptosis in the pancreas. In vitro experiments also showed that ROT decreased STZ- and inflammatory cytokines-induced β-cell apoptosis. These protective effects were accompanied by attenuation of reactive oxygen species, increased mitochondrial membrane potential, and upregulation of transcriptional coactivator PPARα coactivator 1α (PGC-1α)-controlled mitochondrial biogenesis. These findings suggest that mitochondrial complex I inhibition may represent a promising strategy for β-cell protection in T1DM.

中文翻译：

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鱼藤酮可防止β细胞凋亡并减轻1型糖尿病。

1型糖尿病（T1DM）是由胰腺β细胞功能障碍和细胞凋亡引起的，并因此导致严重的胰岛素缺乏。因此，β细胞保护可能是T1DM治疗的主要靶标。有证据表明，线粒体功能缺陷在胰腺β细胞功能障碍和细胞凋亡中起重要作用。然而，线粒体复合体I对β细胞和T1DM的基本作用尚不清楚。在当前的研究中，在链脲佐菌素（STZ）诱导的T1DM小鼠模型和培养的小鼠胰腺β细胞系Min6中评估了复合物I抑制剂鱼藤酮（ROT）的胰腺保护作用及其潜在机制。ROT治疗具有降血糖作用，恢复了胰岛素水平，并减少了胰腺的炎症和细胞凋亡。体外实验还显示，ROT减少了STZ和炎症性细胞因子诱导的β细胞凋亡。这些保护作用伴随着活性氧的减弱，线粒体膜电位的增加以及转录共激活因子PPARα共激活因子1α（PGC-1α）控制的线粒体生物发生的上调。这些发现表明线粒体复合物I的抑制可能代表了T1DM中β细胞保护的有前途的策略。