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The role of mitochondria-derived reactive oxygen species in the pathogenesis of diabetic complications

Research Project

Project/Area Number 13671195
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionKumamoto University

Principal Investigator

TOYONAGA Tetsushi  Kumamoto University, Department of Medicine, Assistant, 医学部, 助手 (60295128)

Co-Investigator(Kenkyū-buntansha) ARAKI Eiichi  Kumamoto University, Department of Medicine, Professor, 医学部, 教授 (10253733)
MIYAMURA Nobuhiro  Kumamoto University, University Hospital, Assistant, 医学部附属病院, 講師 (40274716)
NISHIKAWA Takeshi  Kumamoto University, Department of Medicine, Assistant, 医学部, 助手 (70336212)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsDiabetic complications / Oxidative stress / Mitochondria / 8-hydroxydeoxyguanosine / Manganese superoxide dismutase / トランスジェニックマウス / 糖尿病 / 血管合併症 / 活性酸素
Research Abstract

Recently we proposed that hyperglycemia-induced ROS production from mitochondria is a key event in the development of diabetic complications (Nishikawa et al. 2000; Nature 404: 787-90). During 2001-2002, we have performed below project based on our hypothesis.
Objective - To evaluate urinary 8-hydroxydeoxyguanosine as a marker for the progression of diabetic macroangiopathic complications.
Research design and methods - The content of urinary 8-hydroxydeoxyguanosine (8-OHdG), common carotid intima-media thickness (IMT), the coronary heart disease (CHD) risk score, the severity of diabetic retinopathy, and urinary albumin excretion were examined in 96 patients with type 2 diabetes mellitus including 32 patients, who had been nominated for Kumamoto Study (Shichiri M, et al, Diabetes Care 23 Suppl 2:B21-29, 2000). In addition, the patients from Kumamoto were further evaluated the effect of intensive insulin therapy on urinary 8-OHdG excretion.
Results - The urinary 8-OHdG/creatinine ratio (U8-OHdG) was 2.5 fold elevated in patients with increased HbA1c compared to those with normal HbA1c (p<0.05). In addition, U8-OHdG was 2.3 fold elevated in patients with increased IMT (p<0.005). A similar result was observed between U8-OHdG and CHD risk score (p<0.01). U8-OHdG was significantly elevated in patients with simple retinopathy (p<0.05) and those with advanced retinopathy (p<0.01) compared to patients without retinopathy. Similarly, U8-OHdG was significantly elevated in patients with albuminuria (p<0.01). Furthermore, U8-OHdG was significantly lower in multiple insulin injection therapy group compared with conventional insulin injection therapy group in patients from Kumamoto Study (p<0.01).
Conclusions - Hyperglycemia suggested to be independently increase 8-OHdG in type 2 diabetic patients. 8-OHdG is a useful biomarker of not only microvascular but also microvascular complications in patients with type 2 diabetes.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Takeshi Nishikawa et al.: "Evaluation of urinary 8-hydroxydeoxyguanosine as a novel biomaker of macrovascular complications in type 2 diabetes"Diabetes Care. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 西川武志等: "ミトコンドリア機能異常と細胞内酸化ストレス"血管医学 Vascular Biology & Medicine. 2. 39-46 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 西川武志等: "ミトコンドリアと糖尿病性血管合併症"内分泌・糖尿病科. 13. 469-477 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 西川武志等: "高血糖による酸化ストレス増強機序.ミトコンドリア電子伝達系"Diabetes Frontier. 13. 179-183 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 西川武志等: "ミトコンドリア電子伝達系と糖尿病合併症"分子糖尿病学の進歩. 148-155 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishikawa T, Sasahara T, Kiritoshi S, Sonoda K, Senokuchi T, Matsuo T, Kukidome D, Wake N, Matsumura T, Miyamura N, Sasakida M, Kishikawa H, Araki E: "Evaluation of urinary 8-hydroxydeoxyguanosine as a novel biomarker of macrovascular complications in type 2 diabetes"Diabetes Care. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeshi Nishikawa et al.: "Evaluation of urinary 8-hydroxydeoxyguanosine as a novel biomaker of macrovascular complications in type 2 diabetes"Diabetes Care. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 荒木栄一, 親泊政一, 西川武志: "細胞内ストレス-糖尿病及び合併症の成因として-"Diabetes in the News. 287. (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 西川武志, Michael Brownlee, 荒木栄一: "ミトコンドリア電子伝達系と糖尿病合併症"分子糖尿病学の進歩. 148-155 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 西川武志, 切通伸介, 園田和洋, 松村剛, 荒木栄一: "高血糖による酸化ストレス増強機序.ミトコンドリア電子伝達系"Diabetes Frontier. 13. 179-183 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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