Identification of the mechanism of the development of insulin resistance in androgen deficiency

• Project/Area Number: 24591339
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: FUKUI Michiaki 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (30247829)
• Co-Investigator(Kenkyū-buntansha): HASEGAWA Goji 京都府立医科大学, 医学研究科, 准教授 (00295643) ; NAKAMURA Naoto 京都府立医科大学, 医学研究科, 教授 (40227921) ; SOH Jintetsu 明治国際医療大学, 医学研究科, 教授 (40305587) ; YAMAZAKI Masahiro 京都府立医科大学, 医学研究科, 助教 (50309134)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アンドロゲン / インスリン抵抗性 / 脂肪肝 / 糖輸送担体

Outline of Final Research Achievements

Body weight with orchidectomized mice fed high fat diet increased more than those with sham operation. In addition, The capacity of glucose tolerance worsened more in orchidectomized mice compared with that in sham operation. Orchidectomized mice fed high fat diet had developed fatty liver and insulin resistance due to lipid gene abnormalities in the liver.
We have identified that abnormality of lipid metabolism in the liver and impairment of glucose intake via glucose transporter 4 in peripheral tissue have important roles in the development of insulin resistance.

Research Products

• [Journal Article] Testosterone deficiency induces markedly decreased serum triglycerides, increased small dense LDL, and hepatic steatosis mediated by dysregulation of lipid assembly and secretion in mice fed a high-fat diet. (2013)
  • Author(s): Senmaru T, Fukui M, Okada H, Mineoka Y, Yamazaki M, Tsujikawa M, Hasegawa G, Kitawaki J, Obayashi H, Nakamura N.
  • Journal Title: Metabolism Volume: 60 Issue: 6 Pages: 851-860
  • DOI: 10.1016/j.metabol.2012.12.007
  • Peer Reviewed
• [Presentation] Testosterone Deficiency Exacerbates High-Fat Diet-Induced Glucose Intolerance through Inhibition of GLUT4-Mediated Glucose Uptake in Skeletal Muscle. (2014)
  • Author(s): Mitsuhashi K, Fukui M, Senmaru T, Tsujikawa M, Obayashi H, Fukuda T, Iwase H, Okada H, Tanaka M, Yamazaki M, Hasegawa H, Nakamura N.
  • Organizer: 74th Scientific Session of the America Diabetes Association.
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-06-13 – 2014-06-17
• [Presentation] Testosterone低下マウスの骨格筋におけるGLUT4 translocationシグナル伝達機構の検討 (2014)
  • Author(s): 千丸貴史, 福井道明, 三橋一輝, 福田拓也, 岡田博史, 辻川宗男, 尾林博, 山﨑真裕, 長谷川剛二, 中村直登
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大坂
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] テストステロンによる脂肪細胞におけるグルコース取り込みとそのシグナル伝達機構 (2014)
  • Author(s): 三橋一輝、福井道明、千丸貴史、福田拓也、岡田博史、辻川宗男、尾林博、山﨑真裕、長谷川剛二、中村直登
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大坂
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] Testosterone Deficiency Exacerbates High-Fat Diet-Induced Glucose Intolerance through Inhibition of GLUT4-Mediated Glucose Uptake in Skeletal Muscle. (2014)
  • Author(s): Kazuteru Mitsuhashi, Michiaki Fukui, Takafumi Senmaru, Muneo Tsujikawa, Hiroshi Obayashi, Takuya Fukuda, Hiroya Iwase, Hiroshi Okada, Muhei Tanaka, Masahiro Yamazaki, Goji Hasegawa, Naoto Nakamura.
  • Organizer: 74th Scientific Session of the American Diabetes Association.
  • Place of Presentation: San Francisco, USA
• [Presentation] Testosterone低下マウスの骨格筋におけるGLUT4 translocationシグナル伝達機構の検討． (2014)
  • Author(s): 千丸貴史、福井道明、三橋一輝、福田拓也、岡田博史、辻川宗男、尾林博、山﨑真裕、長谷川剛二、中村直登．
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
• [Presentation] テストステロンによる脂肪細胞におけるグルコース取り込みとそのシグナル伝達機構． (2014)
  • Author(s): 三橋一輝、福井道明、千丸貴史、福田拓也、岡田博史、辻川宗男、尾林博、山﨑真裕、長谷川剛二、中村直登．
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪
• [Presentation] Impaired GLUT4-mediated glucose uptake in skeletal muscle plays a key role in the development of glucose intolerance induced by testosterone deficiency. (2013)
  • Author(s): Takafumi Senmaru, Michiaki Fukui, Kazuteru Mitsuhashi, Takuya Fukuda, Hiroshi Okada, Muneo Tsujikawa, Hiroshi Obayashi, Muhei Tanaka, Mai Asano, Masahiro Yamazaki, Goji Hasegawa, Naoto Nakamura.
  • Organizer: 49th EASD Annual Meeting.
  • Place of Presentation: Barcelona, Spain
• [Presentation] Orchiectomized mice fed a high-fat diet exhibit impaired glucose tolerance due to increased glucose production in liver and decreased glucose uptake in skeletal muscle. (2013)
  • Author(s): Senmaru T, Fukui M, Mitsuhashi K, Okada H, Mineoka Y, Tsujilawa M, Obayashi H, Asano M, Yamazaki M, Hasegawa G, Nakamura N.
  • Organizer: 73rd Scientific Session of the American Diabetes Association.
  • Place of Presentation: Chicago, USA
• [Presentation] Significance of androgen in patients with type 2 diabetes (2013)
  • Author(s): Fukui M
  • Organizer: The 14th Biennial Meeting of the Asia-Pacific Society for Sexual Medicine
  • Place of Presentation: Kanazawa, Japan
  • Invited
• [Presentation] アンドロゲン低下による脂質恒常性破綻を介した耐糖能異常発症機構 (2013)
  • Author(s): 千丸貴史，福井道明，三橋一輝，岡田博史，峠岡佑典，辻川宗男，尾林 博，浅野麻衣，山﨑真裕，長谷川剛二，中村直登
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台
• [Presentation] テストステロン低下は高脂肪食投与マウスの脂肪肝および耐糖能障害を悪化させる (2013)
  • Author(s): 千丸貴史，福井道明，三橋一輝，岡田博史，峠岡佑典，辻川宗男，尾林 博，浅野麻衣，山﨑真裕，長谷川剛二，中村直登
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] 男性ホルモンと糖尿病 (2013)
  • Author(s): 福井道明，岡田博史，千丸貴史，浅野麻衣，山﨑真裕，長谷川剛二，中村直登
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] Impaired hepatic lipid homeostasis plays a key role in the development of glucose intolerance induced by testosterone deficiency. (2012)
  • Author(s): Senmaru T, Fukui M, Obayashi H, Okada H, Mineoka Y, Asano M, Yamazaki M, Hasegawa G, Nakamura N.
  • Organizer: 48th EASD Annual Meeting.
  • Place of Presentation: Berlin, Germany
• [Presentation] アンドロゲン低下は肝臓インスリン抵抗性を増強する (2012)
  • Author(s): 千丸貴史，福井道明，岡田博史，峠岡佑典，岩瀬広哉，浅野麻衣，山﨑真裕，尾林 博，長谷川剛二，中村直登
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜