• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

In vivo metabolomic analysis and metabolic alteration-targeted treatment on diabetic nephropathy model .

Research Project

Project/Area Number 16K07203
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Genome biology
Research InstitutionKeio University

Principal Investigator

KUBO Akiko  慶應義塾大学, 医学部(信濃町), 特任助教 (50455573)

Co-Investigator(Kenkyū-buntansha) 宮下 和季  慶應義塾大学, 医学部(信濃町), 特任准教授 (50378759)
Research Collaborator FUJII Kentaro  
SATO Masaaki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsイメージング質量分析 / メタボロミクス / 代謝 / 糖尿病性腎症 / メタボローム / 質量分析 / 栄養学
Outline of Final Research Achievements

This study aims to find out how the diabetic nephropathy starts by analyzing local energy metabolism in situ. At first, we develop the method to visualize energy metabolism with healthy mice. The quantitative analyses with capillary-electrophoresis mass spectrometry combined with MALDI imaging mass spectrometry allowed us to know local metabolite contents of a frozen section. Then we compared the local energy metabolism between healthy mouse group and model disease mouse group.
When the energy metabolism status is low, ATP decreases and catabolic products such as hypoxanthine and xanthine increases. Hypoxanthine is converted into uric acid by xanthine oxidase which uses O2 molecule and produces reactive oxygen species (ROS). We tried to prevent ROS production in murine kidney by adding xanthine oxidase inhibitor, and analyzed murine energy metabolism. Successfully xanthine oxidase inhibitor blocked hypoxanthine catabolism and promoted ATP production via salvage pathway.

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎症の実態をエネルギー代謝の面で評価することは、臨床研究では難しく、腎障害に至る過程の解明が望まれている。この研究では、マウスモデルを用いて、腎臓の領域ごとのエネルギー代謝の可視化解析法を開発し、エネルギー代謝とROSの発生が密接に関係することを明らかにした。エネルギー代謝が分解方向に傾いたときに、痛風の治療に用いられる経口薬を投与することで、腎保護につながることがわかった。今後、心停止からの回復時、腎移植などの際にキサンチンオキシダーゼ阻害剤を投与することで、腎保護効果が期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (11 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Targeting oxygen sensing prolyl hydroxylase (PHD) for metformin-associated lactic acidosis treatment.2017

    • Author(s)
      Oyaizu-Toramaru T, Suhara T, Hayakawa N, Nakamura T, Kubo A, Minamishima S, Yamaguchi K, Hishiki T, Morisaki H, Suematsu M, Minamishima YA
    • Journal Title

      Mol Cell Biol.

      Volume: 37 (16) Issue: 16

    • DOI

      10.1128/mcb.00248-17

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 質量分析イメージング2017

    • Author(s)
      久保亜紀子
    • Journal Title

      Medical Science Digest

      Volume: 43 Pages: 647-648

    • Related Report
      2017 Research-status Report
  • [Presentation] 急性虚血性腎障害におけるフェブキスソタットによるATPブーストを介した腎保護メカニズムのマスイメージングを用いた可視化解析2018

    • Author(s)
      藤井健太郎, 宮下和季, 久保亜紀子, 佐藤正明, 萩原あいか, 井上博之, 竜崎正毅, 末松誠, 伊藤裕
    • Organizer
      第41回日本高血圧学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A semi-quantitative mass imaging technique revealed region-specific alteration of adenylates in the murine kidney after transient ischemia and reno-protective effect of febuxostat by ameliorating ATP levels in the cortex.2018

    • Author(s)
      藤井健太郎, 宮下和季, 久保亜紀子, 佐藤正明, 萩原あいか, 井上博之, 竜崎正毅, 末松誠, 伊藤裕
    • Organizer
      第61回日本腎臓学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] キサンチンオキシダーゼ阻害による虚血腎保護メカニズムのマスイメージングを用いた可視化解析2018

    • Author(s)
      藤井健太郎, 宮下和季, 久保亜紀子, 佐藤正明, 萩原あいか, 井上博之, 竜崎正毅, 末松誠, 伊藤裕
    • Organizer
      第91回日本内分泌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Febuxostat exerted reno-protective effects after transient ischemia by promoting ATP recovery in the cortex: visualization of renal adenine nucleotides by an imaging mass-spectrometry technique2018

    • Author(s)
      K. Miyashita, K. Fujii, A. Kubo, M. Sato, A. Hagiwara, H. Inoue, M. Suematsu, H. Itoh
    • Organizer
      27th Scientific Meeting of International Society of Hypertension,
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A mass imaging technique revealed a reno-protective effect of the xanthine oxidase inhibitor febuxostat in the ischemic kidney by promoting ATP recovery in the cortex2018

    • Author(s)
      K. Miyashita, K. Fujii, A. Kubo, M. Sato, A. Hagiwara, H. Inoue, M. Suematsu, H. Itoh
    • Organizer
      28th Scientific Meeting of European Society of Hypertension
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A SEMI-QUANTITAIVE IMAGING MASS SPECTROMETRY REVEALED THE RENO-PROTECTIVE EFFECT OF FEBUXOSTAT IN THE ISCHEMIC KIDNEY BY PROMOTING ATP RECOVERY IN THE CORTEX.2018

    • Author(s)
      K. Fujii, K. Miyashita, A. Kubo, M. Sato, A. Hagiwara, H. Inoue, M. Suematsu, H. Itoh
    • Organizer
      55th ERA-EDTA congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MALDI質量分析イメージング法によるマウス急性腎虚血におけるアデニル酸代謝解析2016

    • Author(s)
      久保亜紀子・藤井健太郎・宮下和季・菱木貴子・伊藤 裕・末松 誠
    • Organizer
      第89回日本生化学会年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] ACCUMULATION OF ADENOSINE IN THE OUTER STRIPES OF OUTER MEDULLA IN MURINE KIDNEY IDENTIFIED BY MATRIX-ASSISTED LASER DESORPTION/IONIZATION IMAGING MASS SPECTROMETRY.2016

    • Author(s)
      K. Fujii, K. Miyashita, A. Kubo, M. Sato, A. Hagiwara, H. Inoue, M. Suematsu, H. Itoh
    • Organizer
      26th Scientific Meeting of International Society of Hypertension
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dense accumulation of adenosine in the outer stripes of outer medulla in murine kidney identified by microscopic MALDI-imaging mass spectrometry2016

    • Author(s)
      久保亜紀子・藤井健太郎・宮下和季・菱木貴子・伊藤 裕・末松 誠
    • Organizer
      21st International Mass Spectrometry Conference
    • Place of Presentation
      Toronto, canada
    • Year and Date
      2016-08-20
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 質量分析イメージングによる腎皮髄境界におけるアデノシン集積の発見とアデノシン 集積機構の解析2016

    • Author(s)
      藤井 健太郎, 宮下 和季, 久保 亜紀子, 佐藤 正明, 萩原 あいか, 井上 博之, 末松 誠, 伊藤 裕
    • Organizer
      第59回 日本腎臓学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 質量分析イメージングが解く腎アデニル酸代謝のパラドクス2016

    • Author(s)
      久保亜紀子・藤井健太郎・中西 豪・宮下和季・伊藤 裕・末松 誠
    • Organizer
      第64回質量分析総合討論会
    • Place of Presentation
      ホテル阪急エキスポパーク(大阪府吹田市)
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2021-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi