Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2016, Article ID 1828071, 17 pages
http://dx.doi.org/10.1155/2016/1828071
Research Article

The Different Effects of Atorvastatin and Pravastatin on Cell Death and PARP Activity in Pancreatic NIT-1 Cells

1Diabetes Research Laboratory, Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan
2Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
3Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan
4Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan
5Graduate Institute of Integrative Medicine, China Medical University, Taichung, Taiwan
6Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

Received 23 January 2016; Revised 28 May 2016; Accepted 29 June 2016

Academic Editor: Hiroshi Okamoto

Copyright © 2016 Ya-Hui Chen 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

Statins have been widely used drugs for lowering low-density lipoprotein and for preventing heart attack and stroke. However, the increased risk for developing diabetes during extended stain use and the molecular mechanisms remain unclear. The objective of this study was to elucidate the signaling pathway and biological function between necrosis and autophagy induced by atorvastatin (AS) and pravastatin (PS). Here we observed that atorvastatin (AS) can increase intracellular reactive oxygen species (ROS) and induce necrotic cell death and autophagy in NIT-1 cells, whereas pravastatin (PS) does not cause ROS and cell death but also induces autophagy. PARP1 exhibited a dual role in modulating necrosis and autophagy in AS- and PS-treated NIT-1 cells through RIP1-RIP3-MLKL pathway and PARP1-AMPK-mTOR pathway. Lastly, AS treatment induced mitochondrial morphology injury significantly more than PS treatment did. Thus, the PARP1 activation should be considered in the development of effective statin therapies for diabetes. Future studies may examine specific mechanisms and pathways in mitochondria, autophagy, and oxidative stress in vivo.