Xiong Xiwen, Sun Xupeng, Wang Qingzhi, Qian Xinlai, Zhang Yang, Pan Xiaoyan, Dong X Charlie
Department of Forensic MedicineXinxiang Medical University, Xinxiang, Henan, China
Department of Forensic MedicineXinxiang Medical University, Xinxiang, Henan, China.
J Endocrinol. 2016 Nov;231(2):159-165. doi: 10.1530/JOE-16-0317. Epub 2016 Sep 6.
Chronic exposure of pancreatic β-cells to abnormally elevated levels of free fatty acids can lead to β-cell dysfunction and even apoptosis, contributing to type 2 diabetes pathogenesis. In pancreatic β-cells, sirtuin 6 (SIRT6) has been shown to regulate insulin secretion in response to glucose stimulation. However, the roles played by SIRT6 in β-cells in response to lipotoxicity remain poorly understood. Our data indicated that SIRT6 protein and mRNA levels were reduced in islets from diabetic and aged mice. High concentrations of palmitate (PA) also led to a decrease in SIRT6 expression in MIN6 β-cells and resulted in cell dysfunction and apoptosis. Knockdown of Sirt6 caused an increase in cell apoptosis and impairment in insulin secretion in response to glucose in MIN6 cells even in the absence of PA exposure. Furthermore, overexpression of SIRT6 alleviated the palmitate-induced lipotoxicity with improved cell viability and increased glucose-stimulated insulin secretion. In summary, our data suggest that SIRT6 can protect against palmitate-induced β-cell dysfunction and apoptosis.
胰腺β细胞长期暴露于异常升高的游离脂肪酸水平会导致β细胞功能障碍甚至凋亡，这是2型糖尿病发病机制的一个因素。在胰腺β细胞中，已证明沉默调节蛋白6（SIRT6）可调节对葡萄糖刺激的胰岛素分泌。然而，SIRT6在β细胞中对脂毒性的反应所起的作用仍知之甚少。我们的数据表明，糖尿病和老年小鼠胰岛中的SIRT6蛋白和mRNA水平降低。高浓度的棕榈酸酯（PA）也导致MIN6β细胞中SIRT6表达降低，并导致细胞功能障碍和凋亡。即使在没有PA暴露的情况下，敲低Sirt6也会导致MIN6细胞凋亡增加以及对葡萄糖刺激的胰岛素分泌受损。此外，SIRT6的过表达减轻了棕榈酸酯诱导的脂毒性，提高了细胞活力，并增加了葡萄糖刺激的胰岛素分泌。总之，我们的数据表明SIRT6可以防止棕榈酸酯诱导的β细胞功能障碍和凋亡。
