Department of Physiology, University of Lausanne, Lausanne, Switzerland.
Diabetes. 2012 May;61(5):1100-11. doi: 10.2337/db11-1221. Epub 2012 Mar 7.
Endoplasmic reticulum (ER) homeostasis alteration contributes to pancreatic β-cell dysfunction and death and favors the development of diabetes. In this study, we demonstrate that HDLs protect β-cells against ER stress induced by thapsigargin, cyclopiazonic acid, palmitate, insulin overexpression, and high glucose concentrations. ER stress marker induction and ER morphology disruption mediated by these stimuli were inhibited by HDLs. Using a temperature-sensitive viral glycoprotein folding mutant, we show that HDLs correct impaired protein trafficking and folding induced by thapsigargin and palmitate. The ability of HDLs to protect β-cells against ER stress was inhibited by brefeldin A, an ER to Golgi trafficking blocker. These results indicate that HDLs restore ER homeostasis in response to ER stress, which is required for their ability to promote β-cell survival. This study identifies a cellular mechanism mediating the beneficial effect of HDLs on β-cells against ER stress-inducing factors.
内质网（ER）稳态改变导致胰腺β细胞功能障碍和死亡，并有利于糖尿病的发展。在这项研究中，我们证明了 HDL 可以保护β细胞免受他普西格拉汀、环匹阿尼酸、棕榈酸、胰岛素过表达和高葡萄糖浓度诱导的 ER 应激。这些刺激物介导的 ER 应激标志物诱导和 ER 形态破坏被 HDL 抑制。使用温度敏感的病毒糖蛋白折叠突变体，我们表明 HDL 纠正了他普西格拉汀和棕榈酸诱导的蛋白运输和折叠受损。Brefeldin A（一种内质网到高尔基体运输阻断剂）抑制了 HDL 保护β细胞免受 ER 应激的能力。这些结果表明，HDL 恢复 ER 稳态以响应 ER 应激，这是其促进β细胞存活能力所必需的。本研究确定了一种细胞机制，介导了 HDL 对β细胞对抗 ER 应激诱导因子的有益作用。
