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Investigation of exercise resistance induced by hepatokine selenoprotein P

Research Project

Project/Area Number 25461334
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionKanazawa University

Principal Investigator

Misu Hirofumi  金沢大学, 医学系, 准教授 (80447680)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsヘパトカイン / 運動抵抗性 / セレノプロテインP / 運動療法 / インスリン抵抗性 / 活性酸素 / 運動療法抵抗性
Outline of Final Research Achievements

We have previously identified selenoprotein P (SeP) as a type 2 diabetes-upregulated hepatokine that induces insulin resistance and hyperglycemia. In this study, we propose a novel pathological concept SeP-induced exercise resistance. We have found out that SeP impairs ROS-induced AMPK phosphorylation in cultured myotubes. SeP knockout mice showed increased sensitivity to exercise training. siRNA screening revealed that LRP1 functions as a SeP receptor in cultured myotubes. This study demonstrates that overproduction of SeP induces exercise resistance by suppressing ROS/AMPK through muscle receptor LRP1. Our study opens the door for inhibitors of SeP/LRP1 axis as new drugs for physical inactivity-associated diseases such as type 2 diabetes.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (28 results)

All 2016 2015 2014 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (19 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results)

  • [Journal Article] Development of a Sol Particle Homogeneous Immunoassay for Measuring Full-Length Selenoprotein P in Human Serum.2016

    • Author(s)
      M. Tanaka, Y. Saito, H. Misu, S. Kato, Y. Kita, Y. Takeshita, T. Kanamori, T. Nagano, M. Nakagen, T. Urabe, T. Takamura, S. Kaneko, K. Takahashi and N. Matsuyama.
    • Journal Title

      J Clin Lab Anal

      Volume: 30 Issue: 2 Pages: 114-122

    • DOI

      10.1002/jcla.21824

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Vildagliptin vs liraglutide as a second-line therapy switched from sitagliptin-based regimens in patients with type 2 diabetes: A randomized, parallel-group study.2015

    • Author(s)
      Takeshita Y, Takamura T, Kita Y, Otoda T, Kato K, Wakakuri H, Yamada M, Misu H, Matsushima Y, Kaneko S
    • Journal Title

      J Diabetes Investig

      Volume: 6 Issue: 2 Pages: 192-200

    • DOI

      10.1111/jdi.12269

    • NAID

      120005774894

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.2015

    • Author(s)
      Kato K, Takeshita Y, Misu H, Zen Y, Kaneko S, Takamura T.
    • Journal Title

      J Diabetes Investig.

      Volume: 6 Issue: 2 Pages: 158-163

    • DOI

      10.1111/jdi.12271

    • NAID

      120005593987

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis.2015

    • Author(s)
      Yamada K, Mizukoshi E, Sunagozaka H, Arai K, Yamashita T, Takeshita Y, Misu H, Takamura T, Kitamura S, Zen Y, Nakanuma Y, Honda M, Kaneko S.
    • Journal Title

      Liver Int.

      Volume: 35(2) Issue: 2 Pages: 582-90

    • DOI

      10.1111/liv.12685

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selenoprotein P as a diabetes-associated hepatokine that impairs angiogenesis by inducing VEGF resistance in vascular endothelial cells.2014

    • Author(s)
      Ishikura K, Misu H, Kumazaki M, Takayama H, Matsuzawa-Nagata N, Tajima N, Chikamoto K, Lan F, Ando H, Ota T, Sakurai M, Takeshita Y, Kato K, Fujimura A, Miyamoto K, Saito Y, Kameo S, Okamoto Y, Takuwa Y, Takahashi K, Kidoya H, Takakura N, Kaneko S, Takamura T
    • Journal Title

      Diabetologia

      Volume: 57 Issue: 9 Pages: 1968-1976

    • DOI

      10.1007/s00125-014-3306-9

    • NAID

      120005463349

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism : a randomised controlled trial2014

    • Author(s)
      Y Takeshita, T Takamura, M Honda, Y Kita, Y Zen, KI Kato, H Misu, T Ota, M Nakamura, K Yamada, H Sunagozaka, K Arai, T Yamashita, E Mizukoshi, S Kaneko
    • Journal Title

      Diabetologia

      Volume: 57(5) Issue: 5 Pages: 878-90

    • DOI

      10.1007/s00125-013-3149-9

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metformin Suppresses Expression of the Selenoprotein P gene via an AMPK-FoxO3a Pathway in H4IIEC3 Hepatocytes2014

    • Author(s)
      H Takayama, H Misu, H Iwama, K Chikamoto, Y Saito, K Murao, A Teraguchi, F Lan, A Kikuchi, R Saito, N Tajima, T Shirasaki, S Matsugo, KI Miyamoto, S Kaneko, T Takamura
    • Journal Title

      J Biol Chem

      Volume: 289(1) Issue: 1 Pages: 335-45

    • DOI

      10.1074/jbc.m113.479386

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance2014

    • Author(s)
      Fei Lan, H Misu, K Chikamoto, H Takayam, A Kikuchi, K Mohri, N Takata, H Hayashi, N Matsuzawa-Nagata, Y Takeshita, H Noda, Y Matsumoto, T Ota, T Nagano, M Nakagen, K Miyamoto, K Takatsuki, T Seo, K Iwayama, K Tokuyama, S Matsugo, H Tang, Y Saito, S Yamagoe, S Kaneko, T Takamura
    • Journal Title

      Diabete

      Volume: 63 Issue: 5 Pages: 1649-1664

    • DOI

      10.2337/db13-0728

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic Fatty liver disease2014

    • Author(s)
      K Kato, T Takamura, Y Takeshita, Y Ryu, H Misu, T Ota, K Tokuyama, S Nagasaka, M Matsuhisa, O Matsui, S Kaneko
    • Journal Title

      PLoS One

      Volume: 9(3) Issue: 3 Pages: e92170-e92170

    • DOI

      10.1371/journal.pone.0092170

    • NAID

      120005440398

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヘパトカインセレノプロテインPは骨格筋受容体LRP1を介して運動療法抵抗性を惹起する2016

    • Author(s)
      高山浩昭, 御簾博文, 菊地晶裕, 石井清朗, 斎藤芳郎, 金子周一, 篁俊成
    • Organizer
      第30回日本糖尿病肥満動物学会
    • Place of Presentation
      大宮ソニックシティ(埼玉)
    • Year and Date
      2016-03-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヘパトカインセレノプロテインPは筋受容体LRP1を介して“運動療法抵抗性”を惹起する2015

    • Author(s)
      高山浩昭, 御簾博文, 斎藤芳郎, 金子周一, 篁俊成
    • Organizer
      第27回分子糖尿病シンポジウム
    • Place of Presentation
      丸ビルホール&コンファレンススクエア(東京)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヘパトカインSePと筋受容体LRP1よる運動感受性制御2015

    • Author(s)
      御簾博文, 高山浩昭, 金子周一, 篁. 俊成
    • Organizer
      第30回日本糖尿病合併症学会
    • Place of Presentation
      愛知県産業労働センターウインクあいち
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Hepatokine selenoprotein P induces exercise resistance via skeletal muscle receptor LRP1.2015

    • Author(s)
      Hirofumi Misu, Toshinari Takamura and Shuichi Kaneko
    • Organizer
      Japan Digestive Disease Week 2015 International Session (Workshop)
    • Place of Presentation
      Grand Prince Hotel New Takanawa (Tokyo)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hepatokine selenoprotein P and skeletal muscle receptor LRP1 induce exercise resistance by inhibition of ROS and AMPK.2015

    • Author(s)
      Hirofumi Misu
    • Organizer
      The 46th NIPS (National Institute of Physiological Science) International Symposium
    • Place of Presentation
      Nagoya Congress Center
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヘパトカインセレノプロテインP血中濃度による運動療法抵抗性の予知に関する検討2015

    • Author(s)
      御簾博文, 田中睦, 斎藤芳郎, 石井清朗, 竹下有美枝, 金森岳広, 赤澤暢彦, 前田清司, 竹越一博, 金子周一, 篁 俊成
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      東京第一ホテル下関 (山口)
    • Year and Date
      2015-05-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヘパトカインselenoprotein P・LECT2による インスリン感受性の制御機構2015

    • Author(s)
      御簾博文
    • Organizer
      第29回日本糖尿病肥満動物学会
    • Place of Presentation
      京都大学
    • Year and Date
      2015-02-14
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 糖尿病関連ヘパトカインセレノプロテインPはVEGF抵抗性を介して血管新生を障害する2014

    • Author(s)
      御簾博文、石倉和秀、高山浩昭、金子周一、篁 俊成
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ヘパトカインセレノプロテインPは AMPK不活化を介して 運動療法の抵抗性を惹起する2014

    • Author(s)
      御簾博文
    • Organizer
      第35回日本肥満学会
    • Place of Presentation
      宮崎シーガイア
    • Year and Date
      2014-10-25
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 2型糖尿病の病態形成における ヘパトカインセレノプロテインPの役割2014

    • Author(s)
      御簾博文
    • Organizer
      第29回日本糖尿病合併症学会
    • Place of Presentation
      東京都市センターホテル
    • Year and Date
      2014-10-03
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 抗酸化ヘパトカインセレノプロテインPはVEGF抵抗性を介して糖尿病性血管新生障害に寄与する2014

    • Author(s)
      御簾博文、石倉和秀、斎藤芳郎、金子周一、篁 俊成
    • Organizer
      第65回日本酸化ストレス学会学術集会
    • Place of Presentation
      同志社大学(京都)
    • Year and Date
      2014-09-05
    • Related Report
      2014 Research-status Report
  • [Presentation] 飽食感知へパトカインLECT2の同定と その機能解析2014

    • Author(s)
      御簾博文、篁 俊成、金子周一
    • Organizer
      第50回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ(東京)
    • Year and Date
      2014-05-29
    • Related Report
      2014 Research-status Report
  • [Presentation] インスリン抵抗性誘導ヘパトカイン セレノプロテインPの 骨格筋における受容体の探索2014

    • Author(s)
      御簾博文、高山浩昭、蘭 菲、 田島奈津美、菊地晶裕、石井清朗、 金子周一、篁 俊成
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      リーガロイヤルホテル大阪
    • Year and Date
      2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 肥満関連へパトカイン LECT2の同定2014

    • Author(s)
      御簾博文、Lan Fei、近本啓太、松郷誠一、高山浩昭、山越智、金子周一、篁 俊成
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2014-04-24
    • Related Report
      2014 Research-status Report
  • [Presentation] A novel role for selenoprotein P in the regulation of insulin sensitivity2014

    • Author(s)
      Hirofumi Misu, Yohiro Saito, Kazuhiko Takahashi, Toshinari Takamura, Shuichi Kaneko.
    • Organizer
      17th Biennial Meeting of Society for Free Radical Research International (SFRRI 2014)
    • Place of Presentation
      Kyoto International Conference Center
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Circulating levels of selenoprotein P predict future hyperglycemia in nondiabetic Japanese people

    • Author(s)
      Hirofumi Misu, Takehiro Kanamori, YumieTakeshita, Yohiro Saito, Mutsumi Tanaka, Shuichi Kaneko, Toshinari Takamura.
    • Organizer
      49th Annual Meeting of the European Association for the Study of Diabetes (EASD2013)
    • Place of Presentation
      Fila de Barcelona's Gran Via exhibition centre, Spain
    • Related Report
      2013 Research-status Report
  • [Presentation] ヘパトカインセレノプロテインPは活性酸素/AMPK/PGC1α経路の抑制を介して”運動療法抵抗性”を誘導する

    • Author(s)
      御簾博文, 蘭 菲, 近本啓太, 高山浩昭, 菊地昌裕, 斎藤芳郎, 金子周一, 篁俊成.
    • Organizer
      第36回日本分子生物学会年次学術集会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] インスリン抵抗性誘導へパトカインセレノプロテインPによる高血糖発症予知に関する検討

    • Author(s)
      御簾博文, 田中睦, 斎藤芳郎, 竹下有美枝, 喜多裕樹, 中源雅俊, 長野亨, 金子周一, 篁 俊成.
    • Organizer
      第56回日本糖尿病年次学術集会
    • Place of Presentation
      熊本市民会館
    • Related Report
      2013 Research-status Report
  • [Presentation] ヘパトカインセレノプロテインPによる運動療法抵抗性発症に関する検討

    • Author(s)
      御簾博文, Lan Fei, 高山浩昭, 金子周一, 篁 俊成.
    • Organizer
      第86回日本内分泌学会学術総会
    • Place of Presentation
      仙台国際会議場
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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