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Palmitic Acid-induced Apoptosis in Pancreatic {beta}-Cells Is Increased by Liver X Receptor Agonist and Attenuated by Eicosapentaenoate.
MedLine Citation:
PMID:  21753123     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Saturated fatty acids are implicated in the development of diabetes via the impairment of pancreatic islet β-cell viability and function. Liver X receptors (LXRs) and eicosapentaenoate (EPA) are known regulators of fatty acid metabolism. However, their roles in the pathogenesis of diabetes remain incompletely understood. The aim of this study was to determine the effects of EPA and the LXR agonist T0901317 on saturated fatty acid (palmitic acid)-induced apoptosis in the insulinoma β-cell line INS-1, a model for insulin-secreting β-cells. T0901317 significantly promoted palmitic acid-induced apoptotic cell death in the INS-1 cells. Consistent with these results, caspase-3 activity and BAX and sterol regulatory element binding protein-1c (SREBP-1c) mRNA levels were markedly increased in INS-1 cells co-administered palmitic acid and T0901317. The production of reactive oxygen species was considerably higher in the cells cultured concurrently with T0901317 and palmitic acid than in the cells incubated with either agent alone. EPA treatment attenuated the cellular death promoted by palmitic acid and T0901317 in the INS-1 cells, disclosing a possible mediating mechanism involving the inhibition of SREBP-1c. Finally, T0901317 up-regulated the palmitic acid-induced expression of p27(KIP1), transforming growth factor beta 1, and SMAD3 proteins in INS-1 cells. These results demonstrate that palmitic acid-induced apoptosis in β-cells is enhanced by T0901317 via the activation of LXRs and is blocked by EPA via the inhibition of SREBP-1c, suggesting that the regulation of lipogenesis and lipotoxicity affecting pancreatic β-cell viability and insulin production may be a unique strategy for diabetes therapy.
Authors:
Huasheng Liang; Yuhua Zhong; Shaobi Zhou; Qingdi Quentin Li
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  In vivo (Athens, Greece)     Volume:  25     ISSN:  1791-7549     ISO Abbreviation:  In Vivo     Publication Date:    2011 Sep-Oct
Date Detail:
Created Date:  2011-07-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8806809     Medline TA:  In Vivo     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  711-8     Citation Subset:  IM    
Affiliation:
Beihai Institute of Endocrine and Metabolic Diseases, Ninth Hospital of Guangxi Medical University, Beihai 536000, P. R. China. E-mail: zhongyh111@163.com, or Dr. Qingdi Quentin Li, National Institutes of Health, Building 10, Room 11N234, Bethesda, MD 20892, U.S.A. liquenti@niaid.nih.gov.
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