Elucidation of the role of TFG in glucose and lipid metabolism in pancreas, liver and adipose tissue

• Project/Area Number: 15H06427
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: Hiroshima University
• Principal Investigator: Yamamotoya Takeshi 広島大学, 医歯薬保健学研究院(医), 助教 (50760013)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 糖尿病 / インスリン分泌 / TFG / 脂質代謝 / 細胞内小胞輸送

Outline of Final Research Achievements

To elucidate the role of TFG in insulin secretion, we generated pancreatic β-cell specific TFG knockout mice (βTFG KO) and analyzed the phenotype. βTFG KO displayed marked hyperglycemia with impaired insulin secretion on glucose tolerance test. Impairment of both β-cell mass and function was suggested by smaller insulin-positive area in the immunohistochemical analysis of the pancreas and reduced insulin secretion on glucose stimulation in isolated islets. Electron microscopic observation and microarray gene expression analysis revealed smaller insulin crystal diameters, mild ER stress and downregulation of Nrf2 and its downstream genes as possible underlying mechanisms for the impaired β-cell mass and function in βTFG KO.

Research Products

• [Journal Article] Reduced SHARPIN and LUBAC formation may contribute to CCl4- or acetaminophen-induced liver cirrhosis in mice. (2017)
  • Author(s): Yamamotoya T, Nakatsu Y, Matsunaga Y, Fukushima T, Yamazaki H, Kaneko S, Fujishiro M, Kikuchi T, Kushiyama A, Tokunaga F, Asano T, and Sakoda H.
  • Journal Title: Int. J. Mol. Sci. Volume: 18 Issue: 2 Pages: 326-326
  • DOI: 10.3390/ijms18020326
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as Atherosclerosis and Nonalcoholic Steatohepatitis. (2016)
  • Author(s): Kushiyama A, Nakatsu Y, Matsunaga Y, Yamamotoya T, Mori K, Ueda K, Inoue Y, Sakoda H, Fujishiro M, Ono H, Asano T.
  • Journal Title: Mediators Inflamm. Volume: 2016 Pages: 8603164-8603164
  • DOI: 10.1155/2016/8603164
  • Peer Reviewed / Open Access
• [Journal Article] Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations. (2016)
  • Author(s): Nakatsu Y, Matsunaga Y, Yamamotoya T, Ueda K, Inoue Y, Mori K, Sakoda H, Fujishiro M, Ono H, Kushiyama A, Asano T.
  • Journal Title: Int J Mol Sci. Volume: 17 (9) Issue: 9 Pages: 1495-1495
  • DOI: 10.3390/ijms17091495
  • Peer Reviewed / Open Access
• [Presentation] 膵β細胞におけるTrk-fused gene (TFG) の役割 (2016)
  • Author(s): 山本屋 武、中津 祐介、松永 泰花、櫛山 暁史、石原 寿光、浅野 知一郎
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] Trk-fused gene (TFG) の膵β細胞における役割の解明 (2016)
  • Author(s): 山本屋 武、中津 祐介、 迫田 秀之、藤城 緑、山崎 広貴、菊池 貴子、櫛山 暁史、浅野 知一郎
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
  • Year and Date: 2016-05-19