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Involvement of mitochondrial ROS in the pathogenesis of diabetic complications

Research Project

Project/Area Number 23591312
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NISHIKAWA Takeshi  熊本大学, 大学院生命科学研究部(医), 准教授 (70336212)

Co-Investigator(Kenkyū-buntansha) KONDO Tatsuya  熊本大学, 大学院生命科学研究部, 助教 (70398204)
KUKIDOME Daisuke  熊本大学, 医学部附属病院, 特任助教 (10555759)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords糖尿病 / 糖尿病合併症 / 活性酸素 / 酸化ストレス / ミトコンドリア / 組織低酸素 / DNA傷害
Research Abstract

We previously reported that hyperglycemia-induced mitochondrial reactive oxygen species (ROS) is the key event in the pathogenesis of diabetic complications. In this study, we examined the role of hypoxia-inducible factor-1-alpha (HIF-1alpha) induction in the pathogenesis of diabetic complications, and we clarify that hyperglycemia can progress diabetic complications by the interaction between hyperglycemia-induced mitochondrial ROS and hyperglycemia-induced intracellular hypoxia.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (43 results)

All 2014 2013 2012 2011 Other

All Journal Article (27 results) (of which Peer Reviewed: 16 results) Presentation (16 results) (of which Invited: 2 results)

  • [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
      2013 Annual Research 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
      2013 Annual Research 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
      2013 Annual Research Report
  • [Journal Article] Mechanism-based antioxidant therapies promise to prevent diabetic complications?2013

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

      J Diabetes Invest

      Volume: 4 Pages: 105-107

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages2013

    • Author(s)
      Kinoshita H, Matsumura T, Ishii N, Fukuda K, Senokuchi T, Motoshima H, Kondo T, Taketa K, Kawasaki S, Hanatani S, Takeya M, Nishikawa T, Araki E
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 431 Pages: 124-130

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between lifestyle and lifestyle-related factors in a rural–urban population of Japan2013

    • Author(s)
      Zhang SC, Wei CN, Harada K, Ueda K, Fukumoto K, Matsuo H, Minamoto K, Nishikawa T, Araki E, Ueda A, Fang J
    • Journal Title

      Environ Health Prev Med

      Volume: 18 Pages: 267-274

    • NAID

      10031189203

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of TNFαconverting enzyme activity in visceral adipose tissue of obese mice2013

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

      Biochem Biophys Res Commun

      Volume: 430 Pages: 1189-1194

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association between circulating leukocyte subtype counts and carotid intima-media thickness in Japanese subjects with type 2 diabetes.2013

    • Author(s)
      Matsumura T, Taketa K, Motoshima H, Senokuchi T, Ishii N, Kinoshita H, Fukuda K, Yamada S, Kukidome D, Kondo T, Hisada A, Katoh T, Shimoda S, Nishikawa T, Araki E.
    • Journal Title

      Cardiovascular Diabetology

      Volume: 12(1) Issue: 1 Pages: 177-177

    • DOI

      10.1186/1475-2840-12-177

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 糖尿病大血管障害の治療戦略2013

    • Author(s)
      横手幸太郎, 庄司哲雄, 西川武志, 南野徹
    • Journal Title

      Diabetes Update

      Volume: 2 Pages: 142-153

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 糖尿病合併症の環境因子と体質2013

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

      日本体質医学会

      Volume: 75 Pages: 146-151

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 糖尿病における酸化ストレス制御異常2013

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

      医学のあゆみ

      Volume: 247 Pages: 915-920

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 酸化ストレス.2013

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

      糖尿病性神経障害 基礎から臨床のすべて

      Volume: - Pages: 72-77

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Regulation of TNFα converting enzyme activity in visceral adipose tissue of obese mice2013

    • Author(s)
      川崎修二
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 430 Issue: 4 Pages: 1189-1194

    • DOI

      10.1016/j.bbrc.2012.12.086

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages2013

    • Author(s)
      木下博之
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 431 Issue: 2 Pages: 124-130

    • DOI

      10.1016/j.bbrc.2013.01.014

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between lifestyle and lifestyle-related factors in a rural-urban population of Japan.2013

    • Author(s)
      Zhang SC, Wei CN, Harada K, Ueda K, Fukumoto K, Matsuo H, Minamoto K, Nishikawa T, Araki E, Ueda A, Fang J
    • Journal Title

      Environ Health Prev Med

      Volume: 18 Issue: 4 Pages: 267-274

    • DOI

      10.1007/s12199-012-0315-5

    • NAID

      10031189203

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] レニン・アンギオテンシン系(RAS)を使った網膜症抑制2012

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

      medicina

      Volume: 49 Pages: 876-879

    • Related Report
      2012 Research-status Report
  • [Journal Article] 糖尿病網膜症に対する新規治療法の開発動向2012

    • Author(s)
      西川武志, 後藤秀生, 佐田公範, 久木留大介, 荒木栄一
    • Journal Title

      日本臨床

      Volume: 70(Suppl 5) Pages: 369-373

    • Related Report
      2012 Research-status Report
  • [Journal Article] HbA1cの目標値はどのように設定すべきか2012

    • Author(s)
      植木浩二郎, 傍島裕司, 西川武志, 西村理明, 久木留大介, 柴田大河, 辻野大助
    • Journal Title

      Diabetes Strategy

      Volume: 2 Pages: 169-185

    • Related Report
      2012 Research-status Report
  • [Journal Article] 酸化ストレス2012

    • Author(s)
      西川武志、久木留大介、佐田公範、荒木栄一
    • Journal Title

      糖尿病網膜症のすべて

      Volume: - Pages: 72-77

    • Related Report
      2012 Research-status Report
  • [Journal Article] Caloric restriction decreases ER stress in liver and adipose tissue in ob/ob mice2011

    • Author(s)
      Tsutsumi A, Motoshima H, Kondo T, Kawasaki S, Matsumura T, Hanatani S, Igata M, Ishii N, Kinoshita H, Kawashima J, Taketa K, Furukawa N, Tsuruzoe K, Nishikawa T, Araki E
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 404 Pages: 339-344

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An intervention study to promote self-improvement of lifestyle in a Japanese community : a new health support program2011

    • Author(s)
      Fukumoto K, Wei CN, Matsuo H, Harada K, Zhang SC, Kalay L, Yamashiro T, Nishikawa T, Araki E, Ueda A
    • Journal Title

      Environ Health Prev Med

      Volume: 16 Pages: 253-263

    • NAID

      10029520598

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Telmisartan Exerts Antiatherosclerotic Effects by Activating Peroxisome Proliferator-Activated Receptor-γin Macrophages2011

    • Author(s)
      Matsumura T, Kinoshita H, Ishii N, Fukuda K, Motoshima H, Senokuchi T, Taketa K, Kawasaki S, Nishimaki-Mogami T, Kawada T, Nishikawa T, Araki E
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31 Pages: 1268-1275

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Caloric restriction decreases ER stress in liver and adipose tissue in ob/ob mice.2011

    • Author(s)
      Tsutsumi A, Motoshima H, Kondo T, Kawasaki S, Matsumura T, Hanatani S, Igata M, Ishii N, Kinoshita H, Kawashima J, Taketa K, Furukawa N, Tsuruzoe K, Nishikawa T, Araki E
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 404 Issue: 1 Pages: 339-344

    • DOI

      10.1016/j.bbrc.2010.11.120

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] An intervention study to promote self-improvement of lifestyle in a Japanese community: a new health support program.2011

    • Author(s)
      Fukumoto K, Wei CN, Matsuo H, Harada K, Zhang SC, Kalay L, Yamashiro T, Nishikawa T, Araki E, Ueda A
    • Journal Title

      Environ Health Prev Med

      Volume: 16 Issue: 4 Pages: 253-263

    • DOI

      10.1007/s12199-010-0194-6

    • NAID

      10029520598

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Telmisartan Exerts Antiatherosclerotic Effects by Activating Peroxisome Proliferator-Activated Receptor-{gamma} in Macrophages.2011

    • Author(s)
      Matsumura T, Kinoshita H, Ishii N, Fukuda K, Motoshima H, Senokuchi T, Taketa K, Kawasaki S, Nishimaki-Mogami T, Kawada T, Nishikawa T, Araki E
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31 Issue: 6 Pages: 1268-1275

    • DOI

      10.1161/atvbaha.110.222067

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial reactive oxygen species in the pathogenesis of early diabetic nephropathy

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

      J Diabetes Invest

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association between circulating leukocyte subtype counts and carotid intima-media thickness in Japanese subjects with type 2 diabetes

    • Author(s)
      Matsumura T, Taketa K, Motoshima H, Senokuchi T, Ishii N, Kinoshita H, Fukuda K, Yamada S, Kukidome D, Kondo T, Hisada A, Katoh T, Shimoda S, Nishikawa T, Araki E
    • Journal Title

      Cardiovasc Diabetol

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 各甲状腺ホルモン測定試薬の反応性の相違からFT3偽高値を呈した1例2013

    • Author(s)
      久木留大介,河島淳司,井形元維,近藤龍也,西川武志,荒木栄一
    • Organizer
      第56回日本甲状腺学会学術集会
    • Place of Presentation
      和歌山県民文化会館
    • Related Report
      2013 Final Research Report
  • [Presentation] 高血糖によるミトコンドリア由来活性酸素種(mtROS)と組織内低酸素との関連性2013

    • Author(s)
      佐田公範,西川武志,久木留大介,梶原伸宏,本島寛之,松村剛,荒木栄一
    • Organizer
      第51回日本糖尿病学会九州地方会
    • Place of Presentation
      沖縄コンベンションセンター
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病合併症進展度と小径線維神経における痛覚閾値との関連性2013

    • Author(s)
      佐藤美希,久木留大介,泉香織,狩場宏美,古庄正嗣,守田雄太郎,河島淳司,下田誠也,西川武志,荒木栄一
    • Organizer
      第51回日本糖尿病学会九州地方会
    • Place of Presentation
      沖縄コンベンションセンター
    • Related Report
      2013 Final Research Report
  • [Presentation] Pain threshold values of small fibers are associated with the severity of diabetic complications2013

    • Author(s)
      Kukidome D, Sato M, Shimoda S, Nishikawa T, Araki E
    • Organizer
      49th EASD Annual Meeting 2013
    • Place of Presentation
      Barceló Congresos, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] 小径線維神経における痛覚閾値と糖尿病合併症進展度との関連性2013

    • Author(s)
      久木留大介,佐藤美希,下田誠也,西川武志,荒木栄一
    • Organizer
      第28回日本糖尿病合併症学会
    • Place of Presentation
      旭川グランドホテル(ワークショップ)
    • Related Report
      2013 Final Research Report
  • [Presentation] 酸化ストレスからみた合併症治療の展望2013

    • Author(s)
      西川武志,佐田公範,久木留大介,荒木栄一
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      くまもと県民交流会館パレア(シンポジウム)
    • Related Report
      2013 Final Research Report
  • [Presentation] 酸化ストレスからみた合併症治療の展望2013

    • Author(s)
      西川武志, 佐田公範, 久木留大介, 荒木栄一
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本県民交流館パレア
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 高血糖によるミトコンドリア由来活性酸素種(mtROS)と組織内低酸素との関連性2013

    • Author(s)
      佐田公範, 西川武志, 久木留大介, 梶原伸宏, 本島寛之, 松村剛, 荒木栄一
    • Organizer
      第51回日本糖尿病学会九州地方会
    • Place of Presentation
      沖縄コンベンションセンター
    • Related Report
      2013 Annual Research Report
  • [Presentation] 糖尿病合併症の体質と環境2012

    • Author(s)
      西川武志,荒木栄一
    • Organizer
      第62回日本体質医学会総会
    • Place of Presentation
      大阪国際会議場(シンポジウム)
    • Related Report
      2013 Final Research Report
  • [Presentation] Lifestyle interventions reduce risk factors for metabolic syndrome and improve early insulin responses in subjects with an impaired early insulin response : The impact of early insulin response in Tabaruzaka Study2012

    • Author(s)
      Sada K, Nishikawa T, Yamashiro T, Kukidome D, Isami S, Motoshima H, Matsumura T, Araki E
    • Organizer
      The 72nd Annual Meeting of American Diabetes Association
    • Place of Presentation
      Pennsylvania Convention Center, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Lifestyle interventions reduce risk factors for metabolic syndrome and improve early insulin responses in subjects with an impaired early insulin response: The impact of early insulin response in Tabaruzaka Study2012

    • Author(s)
      Sada K, Nishikawa T, Yamashiro T, Kukidome D, Isami S, Motoshima H, Matsumura T, Araki E
    • Organizer
      American Diabetes Association 72nd Scientific Sessions
    • Place of Presentation
      Pennsylvania Convention Center, アメリカ
    • Related Report
      2012 Research-status Report
  • [Presentation] 糖尿病合併症の体質と環境2012

    • Author(s)
      西川武志, 荒木栄一
    • Organizer
      第62回日本体質医学会総会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 糖尿病性大血管障害と酸化ストレス2011

    • Author(s)
      西川武志,久木留大介,佐田公範,本島寛之,松村剛,荒木栄一
    • Organizer
      第49回糖尿病学会九州地方会
    • Place of Presentation
      アクロス福岡(シンポジウム)
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病網膜症に対する集約的治療の重要性と合併症発症機序に基づく新規治療開発の可能性2011

    • Author(s)
      西川武志,久木留大介,荒木栄一
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌プリンスホテル(シンポジウム)
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病網膜症に対する集約的治療の重要性と合併症発症機序に基づく新規治療開発の可能性,2011

    • Author(s)
      西川武志, 久木留大介, 荒木栄一
    • Organizer
      第54回日本糖尿病学会年次学術集会(招待講演)
    • Place of Presentation
      札幌(札幌プリンスホテル)
    • Related Report
      2011 Research-status Report
  • [Presentation] 糖尿病性大血管障害と酸化ストレス2011

    • Author(s)
      西川武志, 久木留大介, 佐田公範, 本島寛之, 松村剛, 荒木栄一
    • Organizer
      第49回糖尿病学会九州地方会(招待講演)
    • Place of Presentation
      福岡(アクロス福岡)
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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