Metformin Reduces Lipotoxicity-Induced Meta-Inflammation in beta-Cells through the Activation of GPR40-PLC-IP3 Pathway
Metformin Reduces Lipotoxicity-Induced Meta-Inflammation in beta-Cells through the Activation of GPR40-PLC-IP3 Pathway
复制标题
二甲双胍通过激活 GPR40-PLC-IP3 途径减少 β 细胞中脂毒性诱导的元炎症
DOI：
10.1155/2019/7602427
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发表时间：
2019
影响因子：
4.3
通讯作者：
Yang Liyong
中科院分区：
文献类型：
--
作者：
Shen Ximei;Fan Beibei;Hu Xin;Luo Liufen;Yan Yuanli;Yang Liyong
背景和目的。二甲双胍是一种广泛使用的抗糖尿病药物，已被证明具有抗炎特性;然而，其对β细胞Meta炎症的影响仍不清楚。以下研究调查了二甲双胍对β细胞中的Meta炎症的影响以及潜在机制是否与G蛋白偶联受体40-磷脂酶C-三磷酸（GPR 40-PLC-IP 3）途径相关。本研究使用脂毒性诱导的β细胞和高脂饮食诱导的肥胖大鼠模型。二甲双胍降低的脂毒性诱导的β细胞Meta炎症损伤与GPR 40的表达相关。GPR 40参与二甲双胍逆转代谢性炎症关键标志物TLR 4活化介导的β细胞损伤。此外，GPR 40的下游信号蛋白PLC-IP 3参与二甲双胍对Meta炎症的保护作用，二甲双胍的上述过程部分受AMPK活性调节。此外，还观察了二甲双胍对肥胖大鼠的抗炎作用。二甲双胍可以通过调节GPR 40-PLC-IP 3通路和部分通过调节AMPK活性来减少β细胞中脂毒性诱导的Meta性炎症。
Background and Purpose. Metformin, a widely used antidiabetic drug, has been shown to have anti‐inflammatory properties; nevertheless, its influence onβ‐cell meta‐inflammation remains unclear. The following study investigated the effects of metformin on meta‐inflammatory inβ‐cells and whether the underlying mechanisms were associated with the G protein‐coupled receptor 40‐phospholipase C‐inositol 1, 4, 5‐trisphosphate (GPR40‐PLC‐IP3) pathway.Materials and Methods. Lipotoxicity‐inducedβ‐cells and the high‐fat diet‐induced obese rat model were used in the study.Results. Metformin‐reduced lipotoxicity‐inducedβ‐cell meta‐inflammatory injury was associated with the expression of GPR40. GPR40 was involved in metformin reversing metabolic inflammation key marker TLR4 activation‐mediatedβ‐cell injury. Furthermore, downstream signaling protein PLC‐IP3 of GPR40 was involved in the protective effect of metformin on meta‐inflammation, and the above process of metformin was partially regulated by AMPK activity. In addition, the anti‐inflammatory effects of metformin were observed in obese rats.Conclusion. Metformin can reduce lipotoxicity‐induced meta‐inflammation inβ‐cells through the regulation of the GPR40‐PLC‐IP3 pathway and partially via the regulation of AMPK activity.