Xue Li Jun, Huang Qi, Zeng Jiao E, Zhu Hui, Xu Cheng Yan
Department of Endocrinology, The second Clinical Medical college, Yangtze University, Jingzhou, Hubei, 434020, P.R. China.
Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, P.R. China.
Cell Mol Biol (Noisy-le-grand). 2018 Mar 31;64(4):39-45.
The receptor interaction protein 140 (RIP140) cofactor is a key regulator of metabolic balance, but its function in glucose- and lipid-mediated damage in islet β cells is unknown and was investigated in this study. RIP140 expression and distribution was evaluated in MIN6 cells under high glucose and lipid conditions using real-time Polymerase Chain Reaction (PCR), western blotting and confocal laser scanning microscopy. Cells were separately treated with 500 μM palmitic acid and 25 mM glucose when RIP140 expression was upregulated or downregulated, and cell viability, apoptosis rate, the level of oxidative stress and insulin secretion was assessed, as was the expression of related genes. Increased glucose and palmitic acid elevated RIP140 expression and distribution in nuclei. Overexpression of RIP140 promoted apoptosis but inhibited cell viability in MIN6 cells, and basal insulin secretion and glucose-stimulated insulin secretion levels were altered following treatment with glucose and palmitic acid. In addition, oxidative stress was elevated, phosphorylated extracellular signal-regulated kinases 1/2 and uncoupling protein 2 messenger RNA (mRNA) abundance were increased, B-cell lymphoma-2 protein levels were decreased, and peroxisome proliferators activated receptor gamma co-activator 1 alpha, phosphoenolpyruvate carboxykinase , and pancreatic and duodenal homeobox-1 mRNA levels were downregulated. Furthermore, glucolipotoxicity-induced damage was reversed when RIP140 expression was downregulated by small interfering RNA (SiRNA). RIP140 promotes islet β cells damage caused by glucolipotoxicity.
受体相互作用蛋白140（RIP140）辅助因子是代谢平衡的关键调节因子，但其在胰岛β细胞中葡萄糖和脂质介导的损伤中的作用尚不清楚，本研究对此进行了探究。使用实时聚合酶链反应（PCR）、蛋白质免疫印迹法和共聚焦激光扫描显微镜，评估了高糖和高脂条件下MIN6细胞中RIP140的表达和分布。当RIP140表达上调或下调时，细胞分别用500μM棕榈酸和25mM葡萄糖处理，评估细胞活力、凋亡率、氧化应激水平和胰岛素分泌情况，以及相关基因的表达。葡萄糖和棕榈酸水平升高会使RIP140在细胞核中的表达和分布增加。RIP140的过表达促进了MIN6细胞的凋亡，但抑制了细胞活力，并且在用葡萄糖和棕榈酸处理后，基础胰岛素分泌和葡萄糖刺激的胰岛素分泌水平发生了改变。此外，氧化应激升高，细胞外信号调节激酶1/2磷酸化水平和解偶联蛋白2信使核糖核酸（mRNA）丰度增加，B细胞淋巴瘤-2蛋白水平降低，过氧化物酶体增殖物激活受体γ共激活因子1α、磷酸烯醇式丙酮酸羧激酶和胰腺十二指肠同源盒-1 mRNA水平下调。此外，当用小干扰RNA（SiRNA）下调RIP140表达时，糖脂毒性诱导的损伤得到逆转。RIP140促进了糖脂毒性引起的胰岛β细胞损伤。
