To elucidate the role of Epac in glucose and lipid metabolism in liver

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461337
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Nagoya University
• Principal Investigator: Yoshiharu Oshida 名古屋大学, 総合保健体育科学センター, 教授 (10169295)
• Co-Investigator(Kenkyū-buntansha): TOYODA YUKIYASU 名城大学, 薬学部, 准教授 (60103264) ; OZAKI NOBUAKI 名古屋大学, 総合保健体育科学センター, 特任准教授 (70378082)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: グルカゴン / Ｅｐａｃ / 肝糖産生

Outline of Final Research Achievements

Epac is a novel cAMP-binding protein, which is important for cAMP signaling. Here we studied the role of Epac in glucose and lipid metabolism by using primary rat hepatocytes. Epac2 mRNA not but Epac1 mRNA was detected in liver and Western blots analysis showed the expression of Epac2C in liver. Rap1 pull-down assay revealed that glucagon activated Epac pathway in primary hepatocytes. An Epac-specific activator, 8-pCPT-2’-O-Me-cAMP (ESCA) inhibited glucose-induced glycogen storage. Gene expression of key enzymes regulated gluconeogenesis (G6PC and PEPCK) was increased by ESCA treatment. Epac inhibitor ESI-05 did not attenuate glucagon-induced suppression of glycogen storage. On the other hands, glucagon-induced expression of G6PC and PEPCK mRNA was suppressed by pretreatment of ESI-05. These findings suggest that glucagon regulate hepatic glucose metabolism through Epac pathway.

Free Research Field

糖尿病学