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Protective Role of PPARdelta in Lipoapoptosis of Pancreatic ß Cells.
Yang, Yan; Ren, Jiangong; Tong, Yuzhen; Hu, Xuejian; Lv, Qingguo; Tong, Nanwei.
Afiliación
  • Yang Y; Department of Diabetes, The Second Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China.
  • Ren J; Department of Endocrinology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
  • Tong Y; Department of Diabetes, The Second Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China.
  • Hu X; Department of Endocrinology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
  • Lv Q; Department of Diabetes, The Second Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China.
  • Tong N; Department of Endocrinology, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.
Lipids ; 51(11): 1259-1268, 2016 11.
Article en En | MEDLINE | ID: mdl-27631677
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 ß 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 ß 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 anti-apoptotic effects in pancreatic ß 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.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Palmitatos / Apoptosis / PPAR delta / Células Secretoras de Insulina Límite: Animals Idioma: En Revista: Lipids Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Buscar en Google
Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Palmitatos / Apoptosis / PPAR delta / Células Secretoras de Insulina Límite: Animals Idioma: En Revista: Lipids Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos