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Role of mitochondrial ROS generation in the development of diabetic complications

Research Project

Project/Area Number 26461340
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionDepartment of Clinical Research, Nationai Hospital Organization Kumamoto Medical Center (2015-2016)
Kumamoto University (2014)

Principal Investigator

Nishikawa Takeshi  独立行政法人国立病院機構熊本医療センター(臨床研究部), 独立行政法人国立病院機構熊本医療センター(臨床研究部), 診療科医長 (70336212)

Co-Investigator(Kenkyū-buntansha) 荒木 栄一  熊本大学, 大学院生命科学研究部(医), 教授 (10253733)
久木留 大介  熊本大学, 医学部附属病院, 助教 (10555759)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords糖尿病 / 糖尿病合併症 / 活性酸素 / グルカゴン / ミトコンドリア
Outline of Final Research Achievements

We previously proposed that hyperglycemia-induced mitochondrial ROS (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by manganese superoxide dismutase (MnSOD) overexpression. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Thus, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (24 results)

All 2017 2016 2015 2014

All Journal Article (14 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results)

  • [Journal Article] Low glucose induces mitochondrial reactive oxygen species via fatty acid oxidation in bovine aortic endothelial cells.2017

    • Author(s)
      Kajihara N, Kukidome D, Sada K, Motoshima H, Furukawa N, Matsumura T, Nishikawa T, Araki E
    • Journal Title

      Journal of diabetes investigation

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Measurement of small-fiber pain threshold values for the early detection of diabetic polyneuropathy.2016

    • Author(s)
      Kukidome D, Nishikawa T, Sato M, Igata M, Kawashima J, Shimoda S, Matsui K, Obayashi K, Ando Y, Araki E.
    • Journal Title

      Diabet Med

      Volume: 33 Issue: 1 Pages: 62-69

    • DOI

      10.1111/dme.12797

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of advanced glycation end products in “hyperglycemic memory”.2016

    • Author(s)
      Nishikawa T, Araki E
    • Journal Title

      J Diabetes Invest

      Volume: 7 Issue: 3 Pages: 297-299

    • DOI

      10.1111/jdi.12405

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.2016

    • Author(s)
      Sada K, Nishikawa T, Kukidome D, Yoshinaga T, Kajihara N, Sonoda K, Senokuchi1 T, Motoshima H, Matsumura T, Araki E
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 7 Pages: e0158619-e0158619

    • DOI

      10.1371/journal.pone.0158619

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Acetate alters expression of genes involved in beige adipogenesis in 3T3-L1 cells and obese KK-Ay mice2016

    • Author(s)
      Hanatani S, Motoshima H, Takaki Y, Kawasaki S, Igata M, Matsumura T, Kondo T, Senokuchi T, Ishii N, Kawashima J, Kukidome D, Shimoda S, Nishikawa T, Araki E
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 59 Issue: 3 Pages: 207-214

    • DOI

      10.3164/jcbn.16-23

    • NAID

      130005268723

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 糖尿病合併症の疾患概念と分類2016

    • Author(s)
      西川武志
    • Journal Title

      日本臨床

      Volume: 74 Pages: 9-14

    • Related Report
      2015 Research-status Report
  • [Journal Article] ミトコンドリア由来活性酸素2016

    • Author(s)
      西川武志, 久木留大介, 荒木栄一
    • Journal Title

      日本臨床

      Volume: 74 Pages: 67-72

    • Related Report
      2015 Research-status Report
  • [Journal Article] 糖尿病合併症をいかに防ぐか 予防のエビデンスと戦略.2015

    • Author(s)
      西川武志, 荒木栄一
    • Journal Title

      診断と治療

      Volume: 103 Pages: 290-295

    • Related Report
      2015 Research-status Report
  • [Journal Article] 糖尿病合併症をいかに防ぐか 予防のエビデンスと戦略2015

    • Author(s)
      西川武志, 荒木栄一
    • Journal Title

      診断と治療

      Volume: 103 Pages: 290-296

    • Related Report
      2014 Research-status Report
  • [Journal Article] Mitochondrial reactive oxygen species in the pathogenesis of early diabetic nephropathy.2014

    • Author(s)
      Nishikawa T, Brownlee M, Araki E
    • Journal Title

      J Diabetes Invest

      Volume: 6 Issue: 2 Pages: 137-139

    • DOI

      10.1111/jdi.12258

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation.2014

    • Author(s)
      Fukuda K, Matsumura T, Senokuchi T, Ishii N, Kinoshita H, Yamada S, Murakami S, Nakao S, Motoshima H, Kondo T, Kukidome D, Kawasaki S, Kawada T, Nishikawa T, Araki E
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 457 Issue: 1 Pages: 23-20

    • DOI

      10.1016/j.bbrc.2014.12.063

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 個別化医療をめざした血糖コントロール目標―「熊本宣言」の実践をめざし―2014

    • Author(s)
      西川武志, 荒木栄一
    • Journal Title

      プラクティス

      Volume: 31 Pages: 43-50

    • Related Report
      2014 Research-status Report
  • [Journal Article] 抗酸化療法による糖尿病合併症治療の現在と未来2014

    • Author(s)
      西川武志, 久木留大介, 荒木栄一
    • Journal Title

      日本体質医学会

      Volume: 76 Pages: 16-21

    • NAID

      40020028708

    • Related Report
      2014 Research-status Report
  • [Journal Article] 合併症はなぜ起こる2014

    • Author(s)
      西川武志, 荒木栄一
    • Journal Title

      糖尿病診療マスター

      Volume: 12 Pages: 236-239

    • Related Report
      2014 Research-status Report
  • [Presentation] 低血糖による糖尿病合併症増悪機序 -低血糖誘導ミトコンドリア由来活性酸素( mtROS)の関与-.2016

    • Author(s)
      梶原伸宏, 久木留大介, 佐田公範, 本島寛之, 松村剛, 西川武志, 荒木栄一
    • Organizer
      第54回日本糖尿病学会九州地方会
    • Place of Presentation
      かごしま県民交流センター
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 急激な血糖是正による糖尿病網膜症増悪の機序解明-ミトコンドリアROS の関与-.2016

    • Author(s)
      久木留大介, 梶原伸宏, 佐田公範, 本島寛之, 松村剛, 西川武志, 荒木栄一
    • Organizer
      第31回日本糖尿病合併症学会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 合併症予防におけるヘモグロビンA1cの意義と限界2016

    • Author(s)
      西川武志
    • Organizer
      第31回日本糖尿病合併症学会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 低血糖による糖尿病合併症発症増悪機序におけるミトコンドリア由来活性酸素(mtROS)の関与.2016

    • Author(s)
      梶原伸宏, 久木留大介, 佐田公範, 本島寛之, 松村剛, 西川武志, 荒木栄一
    • Organizer
      第66回日本体質医学会総会
    • Place of Presentation
      和歌山県JAビル
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 糖尿病合併症の機序解明―低血糖による糖尿病合併症増悪におけるミトコンドリア由来活性酸素(mtROS)の関与.2016

    • Author(s)
      梶原伸宏, 久木留大介, 佐田公範, 本島寛之, 松村剛, 西川武志, 荒木栄一
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 大血管合併症の発症・進展予防の戦略2015

    • Author(s)
      西川武志
    • Organizer
      第53回日本糖尿病学会九州地方会
    • Place of Presentation
      アクロス福岡
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 合併症予防における血糖管理の意義と展望2015

    • Author(s)
      西川武志
    • 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 Research-status Report
    • Invited
  • [Presentation] Cellular hypoxia and mitochondrial reactive oxygen species may promote hyperglycemic damage in a coordinated manner.2015

    • Author(s)
      Kiminori S, Nishikawa T, Kukidome D, Kajiwara N, Motoshima H, Matsumura T, Araki E
    • Organizer
      the 51st Annual Meeting of the European Association for the Study of Diabetes
    • Place of Presentation
      Stockholmsmässan, Stockholm
    • Year and Date
      2015-09-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 糖尿病合併症と酸化ストレス2015

    • Author(s)
      西川武志
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関市民会館
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 糖尿病と酸化ストレス2014

    • Author(s)
      西川武志
    • Organizer
      第52回日本糖尿病学会九州地方会
    • Place of Presentation
      熊本県民会館パレア
    • Year and Date
      2014-10-31 – 2014-11-01
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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