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Hypoglycemia induces mitochondrial reactive oxygen species production and promotes retinal vascular permeability

Research Project

Project/Area Number 18K15422
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionKumamoto University

Principal Investigator

Kajihara Nobuhiro  熊本大学, 病院, 病院教員 (80814756)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsミトコンドリア由来活性酸素種 / 低血糖 / 糖尿病網膜症 / 脂肪酸酸化 / 網膜血管内皮細胞 / 血管透過性 / ミトコンドリア / 酸化ストレス
Outline of Final Research Achievements

I hypothesized that the mechanisms underlying hypoglycemia-induced diabetic retinopathy are associated with blood-retinal barrier (BRB) breakdown due to mitochondrial reactive oxygen species (mtROS) generation during hypoglycemia. Here, I aimed to determine whether hypoglycemia exacerbated mtROS production and induced BRB disruption. As the results, I observed that hypoglycemia induced mtROS production by increasing fatty acid oxidation (FAO), which was suppressed by overexpression of mitochondrial-specific manganese superoxide dismutase (MnSOD) in retinal endothelial cells. Furthermore, FAO blockade decreased the hypoglycemia-induced mtROS production. Recurrent hypoglycemia increased albumin leak in diabetic mice retina, which was suppressed in diabetic vascular endothelial cell-specific MnSOD transgenic mice.

Academic Significance and Societal Importance of the Research Achievements

低血糖時の網膜血管内皮細胞において脂肪酸酸化亢進を介してmtROS産生が増加すること、また低血糖由来mtROSがBRB破綻の一因になることを世界で初めて示した。低血糖時の脂肪酸酸化亢進の抑制は、低血糖による糖尿病網膜症発症・進展における新たな治療標的となりうると考えられた。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2021 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Hypoglycemia Induces Mitochondrial Reactive Oxygen Species Production Through Increased Fatty Acid Oxidation and Promotes Retinal Vascular Permeability in Diabetic Mice2020

    • Author(s)
      Yoshinaga Ayaka、Kajihara Nobuhiro、Kukidome Daisuke、Motoshima Hiroyuki、Matsumura Takeshi、Nishikawa Takeshi、Araki Eiichi
    • Journal Title

      Antioxidants & Redox Signaling

      Volume: Online ahead of print Issue: 16 Pages: 1245-1259

    • DOI

      10.1089/ars.2019.8008

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 低血糖下の血管内皮細胞における脂肪酸酸化を介したミトコンドリア由来活性酸素種の産生増加-糖尿病合併症新規メカニズムの提唱-2021

    • Author(s)
      梶原伸宏
    • Organizer
      第71回日本体質医学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 低血糖による糖尿病網膜症の発症・進展に対するミトコンドリア由来活性酸素種 (mtROS) の関与2020

    • Author(s)
      吉永礼香,梶原伸宏,久木留大介,本島寛之,松村剛,西川武志,荒木栄一
    • Organizer
      第63回日本糖尿病学会年次学術集会 2020/10/5-16,滋賀 WEB開催,若手研究奨励賞審査口演
    • Related Report
      2020 Research-status Report
  • [Presentation] 脂肪酸酸化を介した低血糖誘導ミトコンドリア由来活性酸素種 (mtROS) の血液網膜関門への影響の検討2020

    • Author(s)
      3.吉永礼香,梶原伸宏,久木留大介,本島寛之,松村剛,西川武志,荒木栄一
    • Organizer
      第35回日本糖尿病合併症学会・第26回日本糖尿病眼学会総会 2020/12/7-21,金沢 WEB開催,ワークショップ
    • Related Report
      2020 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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