Involvement of mitochondrial ROS in the pathogenesis of diabetic complications

• Project/Area Number: 23591312
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kumamoto 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: ¥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.

Research Products

• [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
• [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
• [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
• [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
  • Peer Reviewed
• [Journal Article] Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages (2013)
  • 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
  • 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 Pages: 267-274
  • NAID: 10031189203
  • Peer Reviewed
• [Journal Article] Regulation of TNFαconverting enzyme activity in visceral adipose tissue of obese mice (2013)
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [Journal Article] Regulation of TNFα converting enzyme activity in visceral adipose tissue of obese mice (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages (2013)
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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 Pages: 339-344
  • 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 Pages: 253-263
  • NAID: 10029520598
  • Peer Reviewed
• [Journal Article] Telmisartan Exerts Antiatherosclerotic Effects by Activating Peroxisome Proliferator-Activated Receptor-γin 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 Pages: 1268-1275
  • 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
  • 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
  • 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
  • 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)
  • 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)
  • 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
• [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
• [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
• [Presentation] Pain threshold values of small fibers are associated with the severity of diabetic complications (2013)
  • Author(s): Kukidome D, Sato M, Shimoda S, Nishikawa T, Araki E
  • Organizer: 49th EASD Annual Meeting 2013
  • Place of Presentation: Barceló Congresos, Spain
• [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)
• [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)
• [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
  • Invited
• [Presentation] 高血糖によるﾐﾄｺﾝﾄﾞ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
• [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)
• [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 Study (2012)
  • 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
• [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 Study (2012)
  • 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
• [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
  • 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)
• [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)
• [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）
• [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）