AMPK enhances the expression of pancreatic duo- denal homeobox-1 via PPARa, but not PPARy, in rat insulinoma cell line INS-1  

作　　者：Hua GUO Shui SUN Xu ZHANG Xiu-juan ZHANG Ling GAO Jia-jun ZHAO 

机构地区：[1]Central Laboratory, Provincial Hospital affiliated to Shandong University, Ji'nan 250021, China [2]Department of Orthopedics, Provin- cial Hospital affiliated to Shandong University, Ji'nan 250021, China [3]Institute of Endocrinology, Shandong Academy of Clinical Medi- cine, Provincial Hospital affiliated to Shandong University, Ji'nan 250021, China [4]Department of Pharmacy, the Third affiliated Hospital to Zhengzhou University, Zhengzhou 450052, China

出　　处：《Acta Pharmacologica Sinica》2010年第8期963-969,共7页中国药理学报（英文版）

基　　金：Acknowledgements This study was supported by the National Natural Science Foundation of China （No 30670994 and 30940038） and the Natural Science Foundation of Shandong Province （No Q2006C15）.

摘　　要：Aim： To investigate whether AMP-activated protein kinase （AMPK） regulates the expression of pancreatic duodenal homeobox-1 （PDX- 1）, a β-cell-specific transcription factor and whether PPARa/γ is involved in the regulation of pancreatic β-cell lines after acute stimula- tion. Methods： Rat insulinoma cell line INS-1 was treated with an activator （AICAR） or inhibitor （Compound C） of AMPK as well as inhibitors of PPARs （MK886 to PPARα and BADGE to PPARy）. The mRNA levels of PDX-1, PPARa and PPARy were measured using real-time RT- PCR, and Western blotting was used to detect the protein expression of these factors. Results： Activation of AMPK by AICAR induced significantly increased the expression of PDX-1, and this increase was abrogated when AMPK was inactivated by Compound C. Similarly, the expression of PPARα and PPARy was also increased by AICAR or decreased by Compound C. However AMPK activation did not increase nuclear PDX-1 protein levels when PPARa was inhibited. In contrast, AMPK activation still up-regulated PDX-1 protein levels during PPARy inhibition. Additionally, PPARα activation induced by fenofibrate signifi- cantly enhanced nuclear PDX-1 protein expression. Conclusion： AMPK regulates the expression of PDX-1 at both the transcriptional and protein levels, and PPARα may be acutely involved in the regulation of INS-1 cells.Aim： To investigate whether AMP-activated protein kinase （AMPK） regulates the expression of pancreatic duodenal homeobox-1 （PDX- 1）, a β-cell-specific transcription factor and whether PPARa/γ is involved in the regulation of pancreatic β-cell lines after acute stimula- tion. Methods： Rat insulinoma cell line INS-1 was treated with an activator （AICAR） or inhibitor （Compound C） of AMPK as well as inhibitors of PPARs （MK886 to PPARα and BADGE to PPARy）. The mRNA levels of PDX-1, PPARa and PPARy were measured using real-time RT- PCR, and Western blotting was used to detect the protein expression of these factors. Results： Activation of AMPK by AICAR induced significantly increased the expression of PDX-1, and this increase was abrogated when AMPK was inactivated by Compound C. Similarly, the expression of PPARα and PPARy was also increased by AICAR or decreased by Compound C. However AMPK activation did not increase nuclear PDX-1 protein levels when PPARa was inhibited. In contrast, AMPK activation still up-regulated PDX-1 protein levels during PPARy inhibition. Additionally, PPARα activation induced by fenofibrate signifi- cantly enhanced nuclear PDX-1 protein expression. Conclusion： AMPK regulates the expression of PDX-1 at both the transcriptional and protein levels, and PPARα may be acutely involved in the regulation of INS-1 cells.

关 键 词：AMP-activated protein kinase PPARα PPARY PDX-1 INS-1 cells 

分 类 号：Q969.436.5[生物学—昆虫学] S831.1[农业科学—畜牧学]