Involvement of mitochondrial ROS in the pathogenesis of diabetic complications

2013 Fiscal Year Final Research Report

• 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
• Keywords: 糖尿病 / 糖尿病合併症 / 活性酸素

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] 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
  • 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] 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
  • 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] 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
  • Year and Date: 20131114-16
• [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
  • Year and Date: 20131108-09
• [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
  • Year and Date: 20131108-09
• [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
  • Year and Date: 20130923-27
• [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)
  • Year and Date: 20130913-14
• [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)
  • Year and Date: 20130516-18
• [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)
  • Year and Date: 20121103-04
• [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
  • Year and Date: 20120608-12
• [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)
  • Year and Date: 20111014-15
• [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)
  • Year and Date: 20110519-21