title: HDLs protect pancreatic β-cells against ER stress by restoring protein folding and trafficking.
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.
authors.affiliation: Department of Physiology, University of Lausanne, Lausanne, Switzerland.
authors.forename: Jannick
authors.initials: J
authors.lastname: Pétremand
authors.forename: Julien
authors.initials: J
authors.lastname: Puyal
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Chatton
authors.forename: Jessica
authors.initials: J
authors.lastname: Duprez
authors.forename: Florent
authors.initials: F
authors.lastname: Allagnat
authors.forename: Miguel
authors.initials: M
authors.lastname: Frias
authors.forename: Richard W
authors.initials: RW
authors.lastname: James
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Jonas
authors.forename: Christian
authors.initials: C
authors.lastname: Widmann
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D007340:Insulinoma / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D017510:Protein Folding; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000378:metabolism
chemical_list: D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D014760:Viral Fusion Proteins; D049452:Green Fluorescent Proteins