gpr40与β细胞脂毒性的关系及吡格列酮干预作用分析-relationship between gpr 40 and β -cell lipid toxicity and analysis of pioglitazone intervention effect.docx

4 4 GSIS in pSilencer-control transfected cells, but not in the cells transfected with GPR40shRNA. While 48-h exposure to FFAs significantly impaired GSIS in pSilencer-control transfected cells as well as the cells transfected with GPR40shRNA. Furthermore, pioglitazone enhanced insulin secretion in pSilencer-control transfected cells exposed to FFAs for 48 h, but not in the cells transfected with GPR40shRNA. The third part of this study was to determine the contribution of GPR40 to short- or long-term effects of FFAs and pioglitazone on the expression of PDX-1 and GLUT2 in βTC6 cells. Cells were incubated in 0.5 mmol/L FFAs for 1 h or 48 h, or 10μmol/l pioglitazone or combination of 0.5 mmol/L FFAs and 10μmol/l pioglitazone for 48 h. Results showed that 1-h exposure to FFAs significantly increased expression of PDX-1 and GLUT2 in pSilencer-control transfected cells, but not in the cells transfected with GPR40shRNA. While 48-h exposure to FFAs significantly decreased expression of PDX-1 and GLUT2 in pSilencer-control transfected cells as well as the cells transfected with GPR40shRNA. Furthermore, pioglitazone increased expression of PDX-1 and GLUT2 in pSilencer-control transfected cells exposed to FFAs for 48 h, but not in the cells transfected with GPR40shRNA. These results indicate that GPR40 mediates the short-term effects of FFAs on GSIS and the expression of PDX-1 and GLUT2, but does not mediate the chronic lipotoxicity on β-cells. The reverse role of pioglitazone on lipotoxicity of β-cells may be related to GPR40. Key word: Free fatty acids; GPR40; Short hairpin RNA; βTC6 cells; Insulin secretion；PDX-1；Pioglitazone 2 2 学位论文原创性声明和版权使用授权书 学位论文原创性声明 本人郑重声明：所呈交的学位论文，是本人在导师的指导下，独立进行研究工作所取得 的真实成果。除文中已注明引用的内容外，本论文不含任何其他个人或集体已经发表或撰写 过的作品成果。对本论文的研究做出重要贡献的个人和集体，均已在文中以明确方式标明。 本人完全意识到本声明的法律结果由本人承担。 作者签名（手写）： 导师签名（手写）： 年 月 日  年 月 日 学位论文版权使用授权书 本学位论文作者完全了解学校有关保留、使用学位论文的规定，同意学校保 留并向国家有关部门或机构（如国家图书馆、中国学术期刊电子杂志社的《中国 优秀博硕士学位论文数据库》、中国科学技术信息研究所的《中国学位论文全文 数据库》等）送交论文的复印件