Protective Role of PPARdelta in Lipoapoptosis of Pancreatic beta Cells

doi:10.1007/s11745-016-4190-5

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	Protective Role of PPARdelta in Lipoapoptosis of Pancreatic beta Cells
	Yang, Y; Ren, JG; Tong, YZ; Hu, XJ; Lv, QG; Tong, NW; Tong, NW (reprint author), Sichuan Univ, West China Hosp, Dept Endocrinol, Chengdu 610041, Sichuan, Peoples R China.
刊名	LIPIDS
	2016-11
卷号	51 期号:11 页码:1259-1268
关键词	PPARdelta Pancreatic beta cells GLP-1R Palmitate Apoptosis
ISSN号	0024-4201
DOI	10.1007/s11745-016-4190-5
文献子类	Article
英文摘要	Lipoapoptosis plays an important role in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor delta (PPARdelta), a vital regulator of glucose and lipid metabolism, may reduce fatty acid-induced pancreatic beta cell lipotoxicity in diabetes. However, the detailed molecular mechanisms underlying this process are not fully understood. In this study, we investigated the effect of activation of PPARdelta on palmitate-induced beta cell apoptosis, and we explored the potential mechanism of the antiapoptotic effect. The cell apoptosis was determined by DNA fragmentation analysis and Hoechst 33342 staining. The expressing of glucagon-like peptide-1 receptor (GLP-1R) in INS-1 cells was assessed by Western blotting, quantification of PCR, and was further confirmed by immunofluorescence staining. The potential of PPARdelta to interact with homologous PPRE in the GLP-1R gene was determined by Chromatin immunoprecipitation (ChIP). Our results showed that exposure of INS-1 cells to palmitate for 24 h caused a significant increase in cell apoptosis, which was inhibited by GW501516. PPARdelta exerted antiapoptotic effects in pancreatic beta cells via the PI3 K/PKB/FoxO1 signaling pathway. Moreover, PPARdelta upregulated the GLP-1R expression under lipotoxic conditions. The ChIP assay revealed a direct binding of PPARdelta to a noncanonical PPRE motif of the GLP-1R gene in INS-1 cells. Our study suggested that the anti-apoptotic action of PPARdelta may involve its transcriptional regulation of GLP-1R and PI3 K/PKB/FoxO1 signaling. GW501516 and possible other GW-based strategies may confer additional benefit beyond improved glycemic control. GLP-1R and PI3 K/PKB/FoxO1 signaling. GW501516 and possible other GW-based strategies may confer additional benefit beyond improved glycemic control.
学科主题	Biochemistry & Molecular Biology ; Nutrition & Dietetics
出版地	HEIDELBERG
资助项目	国家自然科学基金项目
项目编号	National Natural Science Foundation of China [81170777]
语种	英语
WOS记录号	WOS:000388184500005
资助机构	NSFC
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/188704]
专题	第二临床医学院_期刊论文
通讯作者	Tong, NW (reprint author), Sichuan Univ, West China Hosp, Dept Endocrinol, Chengdu 610041, Sichuan, Peoples R China.
推荐引用方式 GB/T 7714	Yang, Y,Ren, JG,Tong, YZ,et al. Protective Role of PPARdelta in Lipoapoptosis of Pancreatic beta Cells[J]. LIPIDS,2016,51(11):1259-1268.
APA	Yang, Y.,Ren, JG.,Tong, YZ.,Hu, XJ.,Lv, QG.,...&Tong, NW .(2016).Protective Role of PPARdelta in Lipoapoptosis of Pancreatic beta Cells.LIPIDS,51(11),1259-1268.
MLA	Yang, Y,et al."Protective Role of PPARdelta in Lipoapoptosis of Pancreatic beta Cells".LIPIDS 51.11(2016):1259-1268.