Lipotoxic Stress Induces Pancreatic β-Cell Apoptosis through Modulation of Bcl-2 Proteins by the Ubiquitin-Proteasome System
Joint Authors
Litwak, Sara A.
Wali, Jibran A.
Pappas, Evan G.
Saadi, Hamdi
Stanley, William J.
Varanasi, L. Chitra
Kay, Thomas W. H.
Thomas, Helen E.
Gurzov, Esteban N.
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-05-06
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Pancreatic β-cell loss induced by saturated free fatty acids (FFAs) is believed to contribute to type 2 diabetes.
Previous studies have shown induction of endoplasmic reticulum (ER) stress, increased ubiquitinated proteins, and deregulation of the Bcl-2 family in the pancreas of type 2 diabetic patients.
However, the precise mechanism of β-cell death remains unknown.
In the present study we demonstrate that the FFA palmitate blocks the ubiquitin-proteasome system (UPS) and causes apoptosis through induction of ER stress and deregulation of Bcl-2 proteins.
We found that palmitate and the proteasome inhibitor MG132 induced ER stress in β-cells, resulting in decreased expression of the prosurvival proteins Bcl-2, Mcl-1, and Bcl-XL, and upregulation of the prodeath BH3-only protein PUMA.
On the other hand, pharmacological activation of the UPS by sulforaphane ameliorated ER stress, upregulated prosurvival Bcl-2 proteins, and protected β-cells from FFA-induced cell death.
Furthermore, transgenic overexpression of Bcl-2 protected islets from FFA-induced cell death in vitro and improved glucose-induced insulin secretion in vivo.
Together our results suggest that targeting the UPS and Bcl-2 protein expression may be a valuable strategy to prevent β-cell demise in type 2 diabetes.
American Psychological Association (APA)
Litwak, Sara A.& Wali, Jibran A.& Pappas, Evan G.& Saadi, Hamdi& Stanley, William J.& Varanasi, L. Chitra…[et al.]. 2015. Lipotoxic Stress Induces Pancreatic β-Cell Apoptosis through Modulation of Bcl-2 Proteins by the Ubiquitin-Proteasome System. Journal of Diabetes Research،Vol. 2015, no. 2015, pp.1-16.
https://search.emarefa.net/detail/BIM-1067868
Modern Language Association (MLA)
Litwak, Sara A.…[et al.]. Lipotoxic Stress Induces Pancreatic β-Cell Apoptosis through Modulation of Bcl-2 Proteins by the Ubiquitin-Proteasome System. Journal of Diabetes Research No. 2015 (2015), pp.1-16.
https://search.emarefa.net/detail/BIM-1067868
American Medical Association (AMA)
Litwak, Sara A.& Wali, Jibran A.& Pappas, Evan G.& Saadi, Hamdi& Stanley, William J.& Varanasi, L. Chitra…[et al.]. Lipotoxic Stress Induces Pancreatic β-Cell Apoptosis through Modulation of Bcl-2 Proteins by the Ubiquitin-Proteasome System. Journal of Diabetes Research. 2015. Vol. 2015, no. 2015, pp.1-16.
https://search.emarefa.net/detail/BIM-1067868
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1067868