Hunan Agricultural University, Changsha, China.
Horticulture and Landscape College, Hunan Agricultural University, Changsha, China.
J Cell Physiol. 2019 Jun;234(6):9370-9377. doi: 10.1002/jcp.27621. Epub 2018 Oct 28.
Gymnemic acid I (GA I) is a bioactive component of Gymnema sylvestre. It is an Indian traditional medicinal herb which has antidiabetic effect. However, the molecular mechanism is remaining to be elucidated. Here, we showed that high glucose promoted the rate of apoptosis, GA I decreased the apoptosis under the high glucose stress. Our further study explored that GA I increased the number of autophagosome and the ratio of light chain 3-I (LC3-I)/LC3-II in MIN-6 cells under the normal or high glucose stress by the methods of western blot analysis and immunofluorescence. It induced autophagy flux and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase β-1 (p70 S6K/S6K1), which is a substrate of mTOR. GA I decreased the rate of apoptosis and the activity of caspase-3 under the high glucose stress. The inhibition of apoptosis and caspase-3 activity by GA I were increased after treating with autophagy inhibitor in mouse islet β cells MIN-6. Our data suggested that GA I-induced autophagy protected MIN-6 cells from apoptosis under high glucose stress via inhibition the phosphorylation activity of mTOR.
甘糖素 I（GA I）是匙羹藤的一种生物活性成分。它是一种印度传统药用植物，具有降血糖作用。然而，其分子机制仍有待阐明。在这里，我们发现高葡萄糖促进细胞凋亡，而 GA I 可降低高葡萄糖应激下的细胞凋亡率。我们进一步的研究表明，通过 Western blot 分析和免疫荧光实验，GA I 可增加 MIN-6 细胞在正常或高葡萄糖应激下自噬小体的数量和 LC3-I/LC3-II 的比值。GA I 诱导自噬流，并抑制哺乳动物雷帕霉素靶蛋白（mTOR）和核糖体蛋白 S6 激酶β-1（p70 S6K/S6K1）的磷酸化，后者是 mTOR 的底物。GA I 降低了高葡萄糖应激下细胞的凋亡率和 caspase-3 的活性。在 MIN-6 胰岛β细胞中用自噬抑制剂处理后，GA I 对细胞凋亡和 caspase-3 活性的抑制作用增强。我们的数据表明，GA I 通过抑制 mTOR 的磷酸化活性诱导自噬，从而保护 MIN-6 细胞免受高葡萄糖应激诱导的细胞凋亡。
