1. HDLs protect pancreatic β-cells against ER stress by restoring protein folding and trafficking
- Author
-
Petremand, Jannick, Puyal, Julien, Chatton, Jean-Yves, Duprez, Jessica, Allagnat, Florent, Frias, Miguel, James, Richard W., Waeber, Gerard, Jonas, Jean-Christophe, and Widmann, Christian
- Subjects
High density lipoproteins -- Physiological aspects -- Genetic aspects -- Research ,Endoplasmic reticulum -- Physiological aspects -- Genetic aspects ,Diabetes -- Risk factors -- Development and progression -- Genetic aspects -- Research ,Pancreatic beta cells -- Physiological aspects -- Genetic aspects -- Research ,Health - Abstract
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. Diabetes 61:1100-1111, 2012, Pancreatic β-cells have a highly developed endoplasmic reticulum (ER) that reflects their physiological function as insulin-secreting cells. There is ample evidence indicating that alterations in ER homeostasis in β-cells affect [...]
- Published
- 2012
- Full Text
- View/download PDF