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HDLs Protect Pancreatic β-Cells Against ER Stress by Restoring Protein Folding and Trafficking
- Source :
- Diabetes, vol. 61, no. 5, pp. 1100-1111, Diabetes, DIABETES, Diabetes, Vol. 61, No 5 (2012) pp. 1100-11
- Publication Year :
- 2012
- Publisher :
- American Diabetes Association, 2012.
-
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.
- Subjects :
- Male
Protein Folding
Endocrinology, Diabetes and Metabolism
Apoptosis
Insulinoma/metabolism
Endoplasmic Reticulum
Mice
chemistry.chemical_compound
0302 clinical medicine
Stress, Physiological/physiology
Insulin-Secreting Cells
Endoplasmic Reticulum/physiology
Cells, Cultured
ddc:616
0303 health sciences
Lipoproteins, HDL/genetics/metabolism
Brefeldin A
3. Good health
Cell biology
Transport protein
Protein Transport
Animals
Green Fluorescent Proteins/metabolism
Humans
Insulin-Secreting Cells/cytology
Insulin-Secreting Cells/metabolism
Lipoproteins, HDL/genetics
Lipoproteins, HDL/metabolism
Membrane Proteins/metabolism
Mutation
Rats
Rats, Wistar
Viral Fusion Proteins/metabolism
symbols
Lipoproteins, HDL
Signal Transduction
medicine.medical_specialty
Thapsigargin
Green Fluorescent Proteins
030209 endocrinology & metabolism
Biology
03 medical and health sciences
symbols.namesake
Stress, Physiological
Insulin-Secreting Cells/cytology/metabolism/ultrastructure
Internal medicine
Internal Medicine
medicine
030304 developmental biology
Endoplasmic reticulum
Membrane Proteins
Golgi apparatus
Endocrinology
chemistry
Unfolded protein response
Insulinoma
Viral Fusion Proteins
Homeostasis
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....a5d2aeb5d7bdd135c54c04c9680bfccf