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

doi:10.1371/journal.pone.0132411

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	Inhibition of Calcium Influx Reduces Dysfunction and Apoptosis in Lipotoxic Pancreatic beta-Cells via Regulation of Endoplasmic Reticulum Stress
	Zhou, Yuren 2; Sun, Peng 1,2; Wang, Ting 2; Chen, Kaixian1,2 ; Zhu, Weiliang2 ; Wang, Heyao2
刊名	PLOS ONE
	2015-07-06
卷号	10 期号:7
ISSN号	1932-6203
DOI	10.1371/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.
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关键词	FREE FATTY-ACIDS ; INDUCED ER STRESS ; INSULIN-SECRETION ; GLUCOSE-INSENSITIVITY ; GENE-EXPRESSION ; PALMITATE ; FAILURE ; GPR40 ; ACTIVATION ; MECHANISMS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000358157600263
内容类型	期刊论文
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).