Macrophage hypothesis for exercise-induced muscle qualitative and quntitative changes-

• Project/Area Number: 25350901
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: The University of Tokyo (2014-2015); Juntendo University (2013)
• Principal Investigator: IKEDA Shin-ichi 東京大学, 医学(系)研究科(研究院), 助教 (50534898)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マクロファージ / 運動 / インスリン感受性 / インターロイキン６ / GLUT4 / マトリックスメタロプロテーアゼ / 骨格筋

Outline of Final Research Achievements

Exercise is powerfull tool for preventing metaobolic syndrome and/or type 2 diabetes in human and rodents. However, the moleular mechanisms are largely unknown. I found that anti-inflamattory macrophages were recruited into skeletal muscle after a single bout of exercise,which regulates insulin sensitivity in skeletal muscle. Resident macrophages produced and secreted chemokines which were major contributor to recruit macrophage into skeletal muscle. Recruited macrophages produced interleukine-6 and it increased GLUT4 expression in sleletal muscle cells. This is underlying mechanism of exercise-induced increase in muscle insulin sensitivity.

Research Products

• [Journal Article] Exercise-induced increase in IL-6 level enhances GLUT4 expression and insulin sensitivity in mouse skeletal muscle (2016)
  • Author(s): Shin-ichi Ikeda, Yoshifumi Tamura, Saori Kakehi, Kageumi Takeno, Yoshio Fujitani, Ryuzo Kawamori and Hirotaka Watada
  • Journal Title: Biochem Biophys Res Commun Volume: Apr 1 Issue: 4 Pages: 947-952
  • DOI: 10.1016/j.bbrc.2016.03.159
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet. (2016)
  • Author(s): Kakehi S, Tamura Y, Takeno K, Sakurai Y, Kawaguchi M, Watanabe T, Funayama T, Sato F, Ikeda S, Kanazawa A, Fujitani Y, Kawamori R, Watada H.
  • Journal Title: Am J Physiol Endocrinol Metab. Volume: 310 Issue: 1 Pages: 32-40
  • DOI: 10.1152/ajpendo.00220.2015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Telogen elongation in the hair cycle of ob/ob mice (2015)
  • Author(s): Tasaki N, Minematsu T, Mugita Y, Ikeda S, Nakagami G, Sanada H
  • Journal Title: Bioscience, biotechnology, and biochemistry Volume: 80(1) Issue: 1 Pages: 74-79
  • DOI: 10.1080/09168451.2015.1069693
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pseudomonas aeruginosa quorum-sensing signaling molecule N-3-oxododecanoyl homoserine lactone induces matrix metalloproteinase 9 expression via the AP1 pathway in rat fibroblasts (2015)
  • Author(s): 6.Gojiro Nakagami, Takeo Minematsu, Tomohiro Morohoshi, Takumi Yamane, Toshiki Kanazawa, Lijuan Huang, Mayumi Asada, Takashi Nagase, Shin-ichi Ikeda, Tsukasa Ikeda and Hiromi Sanada
  • Journal Title: Biosci Biotechnol Biochem Volume: Jun 22 Issue: 10 Pages: 1-5
  • DOI: 10.1080/09168451.2015.1056509
  • Peer Reviewed
• [Journal Article] A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice. (2014)
  • Author(s): Zheng, D.M., Bian, Z., Furuya, N., Oliva Trejo, J.A., Takeda-Ezaki, M., Takahashi, K., Hiraoka, Y., Mineki, R., Taka, H., Ikeda, S., Komatsu, M., Fujimura, T., Ueno, T., Ezaki, J.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 456 Issue: 1 Pages: 519-526
  • DOI: 10.1016/j.bbrc.2014.11.118
  • Peer Reviewed / Open Access
• [Journal Article] Association between expression of FABPpm in skeletal muscle and insulin sensitivity in intramyocellular lipid-accumulated nonobese men (2014)
  • Author(s): Kawaguchi M, Tamura Y, Kakehi S, Takeno K, Sakurai Y, Watanabe T, Funayama T, Sato F, Ikeda S, Ogura Y, Saga N, Naito H, Fujitani Y, Kanazawa A, Kawamori R, Watada
  • Journal Title: J Clin Endocrinol Metab Volume: 99 Issue: 9 Pages: 3343
  • DOI: 10.1210/jc.2014-1896
  • Peer Reviewed
• [Journal Article] Effects of sitagliptin on ectopic fat contents and glucose metabolism in type 2 diabetic patients with fatty liver: A pilot study (2014)
  • Author(s): Watanabe T, Tamura Y, Kakehi S, Funayama T, Takeno K, Kawaguchi M, Yamamoto L, Sato F, Ikeda S, Taka H, Fujimura T, Fujitani Y, Kawamori R, Watada H
  • Journal Title: J Diabetes Invest Volume: Mar;6(2) Issue: 2 Pages: 164-72
  • DOI: 10.1111/jdi.12262
  • Peer Reviewed / Open Access
• [Journal Article] PARK2/Parkin-mediated mitochondrial clearance contributes to proteasome activation during slow-twitch muscle atrophy via NFE2L1 nuclear translocation. (2014)
  • Author(s): Furuya N, Ikeda SI, Sato S, Soma S, Ezaki J, Trejo JA, Takeda-Ezaki M, Fujimura T, Arikawa-Hirasawa E, Tada N, Komatsu M, Tanaka K, Kominami E, Ueno T.
  • Journal Title: Autophagy Volume: 10 Issue: 4 Pages: 631-41
  • DOI: 10.4161/auto.27785
  • Peer Reviewed
• [Journal Article] Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle (2013)
  • Author(s): Shin-ichi Ikeda, Yoshifumi Tamura, Saori Kakehi, Kageumi Takeno, Minako Kawaguchi, Takahiro Watanabe, Fumihiko Sato, Takeshi Ogihara, Akiko Kanazawa, Yoshio Fujitani, Ryuzo Kawamori, Hirotaka Watada
  • Journal Title: Biochem Biophys Res Commun Volume: 441 Issue: 1 Pages: 36-41
  • DOI: 10.1016/j.bbrc.2013.10.005
  • Peer Reviewed
• [Journal Article] Role of macrophages in exercise-induced enhancement of insulin sensitivity in skeletal muscle (2013)
  • Author(s): Shin-ichi Ikeda, Yoshifumi Tamura
  • Journal Title: J Phys Fitness Sports Med Volume: 2(2) Pages: 233-236
  • NAID: 10031159043
• [Presentation] PEROXIDASE ACTIVITY DURING WOUND HEALING (2016)
  • Author(s): Aya Kitamura, Takeo Minematsu, Gojiro Nakagami, Shin-ichi Ikeda, Hiromi Sanada
  • Organizer: 5th congress of World Union of Wound Healing Societies
  • Place of Presentation: Florence, Italy
  • Year and Date: 2016-09-25
• [Presentation] アシル基長の異なるアシルホモセリンラクトンのob/obマウスに対する発毛効果の比較検討 (2015)
  • Author(s): 池田真一、峰松健夫、真田弘美
  • Organizer: 第20回日本臨床毛髪学会学術集会
  • Place of Presentation: 総合あんしんセンター（高知県高知市）
  • Year and Date: 2015-12-05
• [Presentation] アシルホモセリンラクトン（AHL）とミノキシジル投与によるマウス背部毛包のNOTCH1経路および-catenin/LEF1経路の活性化 (2015)
  • Author(s): 峰松健夫、池田真一、真田弘美
  • Organizer: 第20回日本臨床毛髪学会学術集会
  • Place of Presentation: 総合あんしんセンター（高知県高知市）
  • Year and Date: 2015-12-05
• [Presentation] 低濃度AHLによる筋線維芽細胞への分化はmTOR経路の活性化を介して生じる (2015)
  • Author(s): 池田真一、峰松健夫、仲上豪二朗、真田弘美
  • Organizer: 第45回日本創傷治癒学会
  • Place of Presentation: JPタワーホール（東京都千代田区）
  • Year and Date: 2015-11-30
• [Presentation] アシル基の鎖長の異なるアシルホモセリンラクトンが角化細胞遊走に及ぼす影響 (2015)
  • Author(s): 麦田裕子、峰松健夫、池田真一、仲上豪二朗、真田弘美
  • Organizer: 第45回日本創傷治癒学会
  • Place of Presentation: JPタワーホール（東京都千代田区）
  • Year and Date: 2015-11-30
• [Presentation] 創傷治癒過程におけるペルオキシダーゼ活性の継時的変化 (2015)
  • Author(s): 北村言、峰松健夫、池田真一、仲上豪二朗、真田弘美
  • Organizer: 第45回日本創傷治癒学会
  • Place of Presentation: JPタワーホール（東京都千代田区）
  • Year and Date: 2015-11-30
• [Presentation] スキンブロッティング法を利用した高強度運動時の局所的筋動態の評価 (2015)
  • Author(s): 禰屋光男，峰松健夫，松林武生，中村真理子，池田真一，後藤大地，土肥美智子
  • Organizer: 第70回日本体力医学会
  • Place of Presentation: 和歌山県民文化会館（和歌山県和歌山市）
  • Year and Date: 2015-09-18
• [Presentation] Exercise-induced transient increase in IL-6 stimulates GLUT4 expression and enhances insulin sensitivity in mouse skeletal muscle (2015)
  • Author(s): Shin-ichi Ikeda. Yoshifumi Tamura, Saori Kakehi, Ryuzo Kawamori and Hirotaka Watada
  • Organizer: 2nd Inaugural International Academy of Sportology
  • Place of Presentation: 順天堂大学（東京都文京区）
  • Year and Date: 2015-09-12
  • Int'l Joint Research
• [Presentation] 運動後に増加するIL-6は筋GLUT4発現増加を介してインスリン感受性を亢進する (2014)
  • Author(s): 池田真一、田村好史、筧沙織、河盛隆造、綿田裕孝
  • Organizer: 第６９回日本体力医学会大会
  • Place of Presentation: 長崎大学
  • Year and Date: 2014-09-19 – 2014-09-21
• [Presentation] 運動による筋インスリン感受性亢進におけるマクロファージの関与 (2013)
  • Author(s): 池田 真一、田村 好史、筧 佐織、河盛 隆造、綿田 裕孝
  • Organizer: 第68回日本体力医学会大会
  • Place of Presentation: 東京
• [Book] 看護理工学 (2015)
  • Author(s): 真田弘美、森武俊ほか
  • Total Pages: 234
  • Publisher: 東京大学出版会