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Journal of Diabetes Research
Volume 2016 (2016), Article ID 4692478, 17 pages
http://dx.doi.org/10.1155/2016/4692478
Research Article

Par-4/NF-κB Mediates the Apoptosis of Islet β Cells Induced by Glucolipotoxicity

1Endocrine Department, The First Affiliated Hospital of the Third Military Medical University, Chong Qing 400038, China
2Outpatient Department, The First Affiliated Hospital of the Third Military Medical University, Chong Qing 400038, China

Received 27 February 2016; Accepted 4 April 2016

Academic Editor: Xin Ma

Copyright © 2016 Wu QiNan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Apoptosis of islet β cells is a primary pathogenic feature of type 2 diabetes, and ER stress and mitochondrial dysfunction play important roles in this process. Previous research has shown that prostate apoptosis response-4 (Par-4)/NF-κB induces cancer cell apoptosis through endoplasmic reticulum (ER) stress and mitochondrial dysfunction. However, the mechanism by which Par-4/NF-κB induces islet β cell apoptosis remains unknown. We used a high glucose/palmitate intervention to mimic type 2 diabetes in vitro. We demonstrated that the high glucose/palmitate intervention induced the expression and secretion of Par-4. It also causes increased expression and activation of NF-κB, which induced NIT-1 cell apoptosis and dysfunction. Overexpression of Par-4 potentiates these effects, whereas downregulation of Par-4 attenuates them. Inhibition of NF-κB inhibited the Par-4-induced apoptosis. Furthermore, these effects occurred through the ER stress cell membrane and mitochondrial pathway of apoptosis. Our findings reveal a novel role for Par-4/NF-κB in islet β cell apoptosis and type 2 diabetes.