Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
Diabetes. 2013 Nov;62(11):3927-35. doi: 10.2337/db13-0251. Epub 2013 Aug 6.
Rhein, an anthraquinone compound isolated from rhubarb, has been shown to improve glucose metabolism disorders in diabetic mice. The mechanism underlying the protective effect of rhein, however, remains unknown. Here, we demonstrate that rhein can protect the pancreatic β-cells against hyperglycemia-induced cell apoptosis through stabilizing mitochondrial morphology. Oral administration of rhein for 8 or 16 weeks in db/db mice significantly reduced fasting blood glucose (FBG) level and improved glucose tolerance. Cell apoptosis assay using both pancreatic sections and cultured pancreatic β-cells indicated that rhein strongly inhibited β-cell apoptosis. Morphological study showed that rhein was mainly localized at β-cell mitochondria and rhein could preserve mitochondrial ultrastructure by abolishing hyperglycemia-induced mitochondrial fission protein dynamin-related protein 1 (Drp1) expression. Western blot and functional analysis confirmed that rhein protected the pancreatic β-cells against hyperglycemia-induced apoptosis via suppressing mitochondrial Drp1 level. Finally, mechanistic study further suggested that decreased Drp1 level by rhein might be due to its effect on reducing cellular reactive oxygen species. Taken together, our study demonstrates for the first time that rhein can serve as a novel therapeutic agent for hyperglycemia treatment and rhein protects pancreatic β-cells from apoptosis by blocking the hyperglycemia-induced Drp1 expression.
大黄素是从大黄中分离得到的一种蒽醌类化合物，已被证明可改善糖尿病小鼠的葡萄糖代谢紊乱。然而，大黄素的保护作用的机制尚不清楚。在这里，我们证明大黄素可以通过稳定线粒体形态来保护胰岛β细胞免受高血糖诱导的细胞凋亡。在 db/db 小鼠中连续口服大黄素 8 或 16 周，可显著降低空腹血糖（FBG）水平并改善葡萄糖耐量。使用胰腺切片和培养的胰岛β细胞进行的细胞凋亡检测表明，大黄素强烈抑制β细胞凋亡。形态学研究表明，大黄素主要定位于β细胞的线粒体，并且大黄素可以通过消除高血糖诱导的线粒体分裂蛋白动力相关蛋白 1（Drp1）表达来维持线粒体超微结构。Western blot 和功能分析证实，大黄素通过抑制线粒体 Drp1 水平来保护胰岛β细胞免受高血糖诱导的凋亡。最后，机制研究进一步表明，大黄素降低 Drp1 水平可能是由于其减少细胞内活性氧的作用。总之，我们的研究首次表明，大黄素可以作为一种治疗高血糖的新型治疗药物，通过阻断高血糖诱导的 Drp1 表达来保护胰岛β细胞免于凋亡。
