葡多酚通过缓解内质网应激改善胰岛β细胞功能的机制

摘要

Objective To explore the effects of grape procyanidins ( GPC) on insulin resistance ( IR) andβ-cell function. Methods GPC was extracted from plants ( crimson grape) , which was administrated to HDF diet induced IR in mice. GRP-78 and CHOP were de-tected to reflect magnitude of endoplasmic reticulum stress ( ERS ) . Long non-coding RNA GAS5 ( lncRNA GAS5 ) and microRNA-346 (miR-346) were also measured. Small interference RNA (siRNA) against lncRNA GAS5 was used to verify the increased levels of lncRNA GAS5 and to explore its role in GRP-78 and miR-346 regulations by GPC. Results GPC lowered blood glucose and released IR, which was accompanied by lower levels of ERS markers of GRP-78 and CHOP. Expression of lncRNA GAS5 was up-regulated while miR-346 was down-regulated by GPC. siRNA-lncRNA GAS5 reversed the GRP-78 and miR-346 down-regulations by GPC. Conclusions GPC could ameliorate IR through attenuation of ERS, which is mediated by up-regulation of lncRNA GAS5 and subsequently inhibition of miR-346.%目的 探讨葡多酚对胰岛素抵抗和胰岛β细胞功能的影响及机制.方法 从克伦生葡萄提取葡多酚后干预高脂(HDF)喂养小鼠和胰岛β细胞株Min-6,检测内质网应激标志蛋白葡萄糖调节蛋白(GRP)-78、CCAAT/增强子结合蛋白同源蛋白(CHOP)、长链非编码RNA(lncRNA)GAS5及microRNA(miR)-346表达.通过小分子RNA干扰(siRNA)下调lncRNA GAS5后验证lncRNA GAS5在葡多酚调节内质网应激和miR-346表达水平中的作用.结果 葡多酚可降低HDF动物血糖并改善胰岛素抵抗;同时抑制HDF导致小鼠胰腺内质网标志物GRP-78及CHOP升高.葡多酚还上调lncRNA GAS5和下调miR-346.siRNA-lncRNA GAS5可抑制葡多酚介导的GRP-78和miR-346下调.结论 葡萄酚通过抑制内质网应激改善胰岛素抵抗和胰岛β细胞,其抑制内质网应激是通过上调lncRNA GAS5继而下调miR-346实现的.