Attenuating effect of silibinin on palmitic acid-induced apoptosis and mitochondrial dysfunction in pancreatic β-cells is mediated by estrogen receptor alpha
Attenuating effect of silibinin on palmitic acid-induced apoptosis and mitochondrial dysfunction in pancreatic β-cells is mediated by estrogen receptor alpha
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雌激素受体α介导水飞蓟宾对棕榈酸诱导的胰腺β细胞凋亡和线粒体功能障碍的减弱作用
DOI：
10.1007/s11010-019-03572-1
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发表时间：
2019-10-01
影响因子：
4.3
通讯作者：
Ikejima，Takashi
中科院分区：
文献类型：
--
作者：
Sun，Yue;Yang，Jing;Ikejima，Takashi
在2型糖尿病的发展过程中，高水平的循环游离脂肪酸常常触发胰腺β细胞功能障碍。水飞蓟宾是水飞蓟提取物（silymarin）的主要成分，具有抗糖尿病作用。本研究旨在确定水飞蓟宾对棕榈酸诱导的大鼠胰腺β细胞系INS-1细胞损伤的保护作用。我们的研究结果表明，水飞蓟宾提高细胞活力，增强胰岛素的合成和分泌，并恢复正常的线粒体功能棕榈酸处理的INS-1细胞。越来越多的证据表明，雌激素受体是参与葡萄糖和脂质代谢的关键分子。我们的研究结果表明，水飞蓟宾上调ERα信号通路的发现，ERα特异性抑制剂取消水飞蓟宾的抗脂毒作用。以上结果提示，水飞蓟宾通过上调ERα通路保护INS-1细胞免于凋亡和线粒体损伤。
High levels of circulating free fatty acids often trigger pancreatic β cell dysfunction during the development of type 2 diabetes. Silibinin, the main component ofSilybum marianumfruit extract (silymarin), is reported to have anti-diabetic effect. This study is designed to determine the protective effect of silibinin on palmitic acid-induced damage in a rat pancreatic β-cell line, INS-1 cells. Our results demonstrate that silibinin improves cell viability, enhances insulin synthesis and secretion, and resumes normal mitochondrial function in palmitic acid-treated INS-1 cells. An accumulating body of evidence has shown that the estrogen receptors are key molecules involved in glucose and lipid metabolism. Our results suggest that silibinin upregulates ERα signaling pathway from the finding that ERα-specific inhibitors abolish the anti-lipotoxic effect of silibinin. In conclusion, these findings suggest that silibinin protects INS-1 cells against apoptosis and mitochondrial damage through upregulation of ERα pathway.