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Inhibition of Calcium Influx Reduces Dysfunction and Apoptosis in Lipotoxic Pancreatic beta-Cells via Regulation of Endoplasmic Reticulum Stress

文献类型：期刊论文

作者Zhou, Yuren2; Sun, Peng1,2; Wang, Ting2; Chen, Kaixian1,2; Zhu, Weiliang2; Wang, Heyao2
刊名PLOS ONE
出版日期2015-07-06
卷号10期号:7
ISSN号1932-6203
DOI10.1371/journal.pone.0132411
文献子类Article
英文摘要Lipotoxicity plays an important role in pancreatic beta-cell failure during the development of type 2 diabetes. Prolonged exposure of beta-cells to elevated free fatty acids level could cause deterioration of beta-cell function and induce cell apoptosis. Therefore, inhibition of fatty acids-induced beta-cell dysfunction and apoptosis might provide benefit for the therapy of type 2 diabetes. The present study examined whether regulation of fatty acids-triggered calcium influx could protect pancreatic beta-cells from lipotoxicity. Two small molecule compounds, L-type calcium channel blocker nifedipine and potassium channel activator diazoxide were used to inhibit palmitic acid-induced calcium influx. And whether the compounds could reduce palmitic acid-induced beta-cell failure and the underlying mechanism were also investigated. It was found that both nifedipine and diazoxide protected MIN6 pancreatic beta-cells and primary cultured murine islets from palmitic acid-induced apoptosis. Meanwhile, the impaired insulin secretion was also recovered to varying degrees by these two compounds. Our results verified that nifedipine and diazoxide could reduce palmitic acid-induced endoplasmic reticulum stress to generate protective effects on pancreatic beta-cells. More importantly, it suggested that regulation of calcium influx by small molecule compounds might provide benefits for the prevention and therapy of type 2 diabetes.
WOS关键词FREE FATTY-ACIDS ; INDUCED ER STRESS ; INSULIN-SECRETION ; GLUCOSE-INSENSITIVITY ; GENE-EXPRESSION ; PALMITATE ; FAILURE ; GPR40 ; ACTIVATION ; MECHANISMS
资助项目Shanghai Natural Science Foundation[14ZR1447700] ; National Natural Science Foundation of China[81473262] ; National Natural Science Foundation of China[81072681] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2012ZX09301001-001] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2013ZX09103001-001]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000358157600263
出版者PUBLIC LIBRARY SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/276472]  
专题药理学第三研究室
通讯作者Wang, Heyao
作者单位1.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Zhou, Yuren,Sun, Peng,Wang, Ting,et al. Inhibition of Calcium Influx Reduces Dysfunction and Apoptosis in Lipotoxic Pancreatic beta-Cells via Regulation of Endoplasmic Reticulum Stress[J]. PLOS ONE,2015,10(7).
APA Zhou, Yuren,Sun, Peng,Wang, Ting,Chen, Kaixian,Zhu, Weiliang,&Wang, Heyao.(2015).Inhibition of Calcium Influx Reduces Dysfunction and Apoptosis in Lipotoxic Pancreatic beta-Cells via Regulation of Endoplasmic Reticulum Stress.PLOS ONE,10(7).
MLA Zhou, Yuren,et al."Inhibition of Calcium Influx Reduces Dysfunction and Apoptosis in Lipotoxic Pancreatic beta-Cells via Regulation of Endoplasmic Reticulum Stress".PLOS ONE 10.7(2015).

入库方式： OAI收割

来源：上海药物研究所

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