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Title

HDLs protect pancreatic β-cells against ER stress by restoring protein folding and trafficking

Authors
Pétremand, Jannick
Puyal, Julien
Chatton, Jean-Yves
Duprez, Jessica
Allagnat, Florent
Waeber, Gérard
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Published in Diabetes. 2012, vol. 61, no. 5, p. 1100-11
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.
Keywords AnimalsApoptosisCells, CulturedEndoplasmic Reticulum/physiologyGreen Fluorescent Proteins/metabolismHumansInsulin-Secreting Cells/cytology/metabolism/ultrastructureInsulinoma/metabolismLipoproteins, HDL/genetics/metabolismMaleMembrane Proteins/metabolismMiceMutationProtein FoldingProtein TransportRatsRats, WistarStress, Physiological/physiologyViral Fusion Proteins/metabolism
Identifiers
PMID: 22399686
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Structures
Research group Lipoprotéines sériques (598)
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PÉTREMAND, Jannick et al. HDLs protect pancreatic β-cells against ER stress by restoring protein folding and trafficking. In: Diabetes, 2012, vol. 61, n° 5, p. 1100-11. https://archive-ouverte.unige.ch/unige:28413

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Deposited on : 2013-06-06

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