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

• 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
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: グルカゴン / Ｅｐａｃ / 肝糖産生 / Epac / 糖新生 / グリコーゲン / 糖代謝

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.

Research Products

• [Presentation] 肝臓におけるEpacの発現とその役割に関する検討 (2015)
  • Author(s): 島田渉、尾崎信暁、高木祐輔、館林光亮、押田芳治、豊田行康
  • Organizer: 第61回日本薬学会東海支部総会・大会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-07-04
• [Presentation] 肝糖代謝におけるEpacの役割 (2015)
  • Author(s): 舘林 光亮,尾崎 信暁,高木 祐輔,島田 渉,押田 芳治,豊田 行康
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 山口県下関市
  • Year and Date: 2015-05-23
• [Presentation] Epacを介した肝糖産生酵素の発現調節について
  • Author(s): 正木猛史、尾崎信暁、高木祐輔、館林光亮、押田芳治、豊田行康
  • Organizer: 第62回日本薬学会東海支部総会・大会
  • Place of Presentation: 名古屋