HDLs Protect Pancreatic β-Cells Against ER Stress by Restoring Protein Folding and Trafficking
- Jannick Pétremand1,
- Julien Puyal2,
- Jean-Yves Chatton2,
- Jessica Duprez3,
- Florent Allagnat4,
- Miguel Frias5,
- Richard W. James5,
- Gérard Waeber4,
- Jean-Christophe Jonas3 and
- Christian Widmann1⇓
- 1Department of Physiology, University of Lausanne, Lausanne, Switzerland
- 2Department of Cellular Biology and Morphology, University of Lausanne, Lausanne, Switzerland
- 3Université Catholique de Louvain, Institute of Experimental and Clinical Research, Pole of Endocrinology, Diabetes and Nutrition, Brussels, Belgium
- 4Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
- 5Lipoprotein Laboratory, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Corresponding author: Christian Widmann, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1221/-/DC1.
- Received September 2, 2011.
- Accepted January 29, 2012.
- © 2012 by the American Diabetes Association.
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