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Elucidation of the effect and mechanism of repeated hypoglycemiaon cardiomyocytes in an animal model of diabetes mellitus

Research Project

Project/Area Number 22590209
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionOita University

Principal Investigator

TESHIMA Yasushi  大分大学, 医学部, 助教 (10457608)

Co-Investigator(Kenkyū-buntansha) SAIKAWA Tetsunori  大分大学, 医学部, 教授 (60145365)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords病態生理 / 血糖変動 / 虚血再灌流障害 / 活性酸素種 / マイクロRNA / 心筋障害
Research Abstract

We investigated whether frequent hypoglycemic episodes increase susceptibility to ischemia/reperfusion in diabetic rat heart and involvement of microRNA (miRNA). Cultured cardiomyocytes were alternately exposed to high (450mg/dL) or low (30mg/dL) glucose concentrations for 5 days. Glucose fluctuations increased levels of reactive oxygen species (ROS) and rendered cardiomyocytes more vulnerable to oxidative stress. For the study in vivo, diabetes mellitus was induced by intravenous injection of streptozotocin and glucose fluctuation was induced by 24-h- fast and insulin injection. Isolated hearts were exposed to 20-min global ischemia/30-min reperfusion. The infarcts were larger in the hearts with glucose fluctuations. Electron microscopy revealed swollen mitochondria with destroyed cristae in diabetic heart, and glucose fluctuations aggravated these changes. Levels of ROS were also increased, and catalase and superoxide dismutase activities were down-regulated by glucose fluctuations. We explored the expression profiles of miRNAs using microarray analysis. The expressions of two miRNAs were more abundant in the hearts exposed to glucose fluctuations. These miRNAs appeared to contribute to decreased activities of antioxidant enzymes and subsequent ROS increase. Fluctuating glucose levels increased ROS generation and enhanced ischemia/reperfusion injury in the diabetic heart. Up-regulated miRNAs might account for the increased ROS by suppressing antioxidant enzymes.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (23 results)

All 2013 2012 2011 2010

All Journal Article (3 results) (of which Peer Reviewed: 1 results) Presentation (20 results)

  • [Journal Article] 糖変動と心疾患2013

    • Author(s)
      手嶋泰之
    • Journal Title

      刊糖尿病

      Volume: Vol.5, No2 Pages: 76-81

    • Related Report
      2012 Final Research Report
  • [Journal Article] Activation of CaMKII as a key regulator of reactive oxygen species production in diabetic rat heart2012

    • Author(s)
      Nishio S, Teshima Y, Takahashi N, Thuc LC, Saito S, Fukui A, Kume O, Fukunaga N, Hara M, Nakagawa M, Saikawa T
    • Journal Title

      J Mol Cell Cardiol

      Volume: 52 Pages: 1103-1111

    • Related Report
      2012 Final Research Report
  • [Journal Article] Activation of CaMKII as a key regulator of reactive oxygen species production in diabetic rat heart2012

    • Author(s)
      Satoru Nishio, Yasushi Teshima, Tetsunori Saikawa
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: (In Press) Issue: 5 Pages: 1103-1111

    • DOI

      10.1016/j.yjmcc.2012.02.006

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Glucose Fluctuations Aggravate the Vulnerability of the Heart Against Ischemia/reperfusion Injury in Diabetic Rat2013

    • Author(s)
      Teshima Y, Takahashi N, Saito S, Kondo K, Fukui A, Nishio S, Nakagawa M, Saikawa T
    • Organizer
      第77回日本循環器学会総会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Glucose Fluctuations in Diabetic Rats Aggravate Cardiac Fibrosis Resulting in Worse Outcomes Including Atrial Fibrillation2013

    • Author(s)
      Saito S, Teshima Y, Takahashi N, Kondo K, Fukui A, Nishio S, Nakagawa M, Saikawa T
    • Organizer
      第77回日本循環器学会総会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Calcineurin plays a key role in diabetes mellitus-induced cardiac fibrosis2013

    • Author(s)
      Nishio S, Teshima Y, Takahashi N, Saito S, Kondo K, Fukui A, Nakagawa M, Saikawa T
    • Organizer
      第77回日本循環器学会総会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Role of microRNAs in glucose fluctuations-induced vulnerability of diabetic heart to ischemia/reperfusion2013

    • Author(s)
      Yasushi Teshima
    • Organizer
      第77回日本循環器学会総会学術集会
    • Place of Presentation
      横浜市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Glucose Fluctuations Aggravate Cardiac Fibrosis Resulting in Worse Outcomes Including Atrial Fibrillation in Diabetic Rats2013

    • Author(s)
      Shotaro Saito
    • Organizer
      第77回日本循環器学会総会学術集会
    • Place of Presentation
      横浜市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 血糖値変動が心筋虚血耐性に及ぼす影響について2012

    • Author(s)
      手嶋泰之、高橋尚彦、西尾諭、江崎かおり、宮崎寛子、中川幹子、犀川哲典
    • Organizer
      第58回日本臨床検査医学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report
  • [Presentation] Glucose Fluctuations Aggravate the Vulnerability of the Heart Against Ischemia/reperfusion Injury in Diabetic Rat2012

    • Author(s)
      Teshima Y, Takahashi N, Saito S, Kondo K, Fukui A, Nishio S, Nakagawa M, Saikawa T
    • Organizer
      9th IDF-WPR Congress 2012
    • Place of Presentation
      Kyoto
    • Related Report
      2012 Final Research Report
  • [Presentation] Glucose Fluctuations Aggravate the Vulnerability of Diabetic Heart Against Ischemia/reperfusion mediated via microRNAs modulation2012

    • Author(s)
      Teshima Y, Takahashi N, Thuc LC, Nishio S, Saito S, Fukui A, Kume O, Nakagawa M Saikawa T
    • Organizer
      American Heart Association Scientific Sessions 2012
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Glucose fluctuations in diabetic rats aggravate cardiac fibrosis resulting in worse outcomes including atrial fibrillation2012

    • Author(s)
      Saito S, Teshima Y, Takahashi N, Fukui A, Kondo K, Nishio S, Nakagawa M, Saikawa T
    • Organizer
      第29回国際心臓研究学会(ISHR)日本部会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] 糖尿病心筋における活性酸素種増加の機序について2012

    • Author(s)
      西尾諭、 手嶋泰之、高橋尚彦、中川幹子、犀川哲典
    • Organizer
      第52回日本臨床化学会学術集会
    • Place of Presentation
      盛岡
    • Related Report
      2012 Final Research Report
  • [Presentation] Calmodulin kinase II induces mitochondrial dysfunction by increasing ROS production in STZ-induced diabetic rat heart2012

    • Author(s)
      Saikawa T, Nishio S, Takahashi N, Thuc LC, Saito S, Fukui A, Kume O, Yufu K, Hara M, Nakagawa M, Teshima Y
    • Organizer
      ESC Congress 2012
    • Place of Presentation
      Munich, Germany
    • Related Report
      2012 Final Research Report
  • [Presentation] 糖尿病心臓におけるカルモジュリンキナーゼを介した活性酸素種増加の機序について2012

    • Author(s)
      西尾諭、 手嶋泰之、高橋尚彦、中川幹子、犀川哲典
    • Organizer
      第22回日本病態生理学会
    • Place of Presentation
      大分
    • Related Report
      2012 Final Research Report
  • [Presentation] Repeated hypoglycemia increases the vulnerability of diabetic heart against ischemia/reperfusion2012

    • Author(s)
      Thuc LC, Teshima Y, Nishio S, Fukui A, Kume O, Nakagawa M, Takahashi N, Saikawa T
    • Organizer
      第76回日本循環器学会総会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] Activation of calmodulin kinase II increases reactive oxygen species in STZ-induced diabetic rat heart2012

    • Author(s)
      Nishio S, Teshima Y, Takahashi N, Thuc LC, Saito S, Fukui A, Kume O, Nakagawa M, Saikawa T
    • Organizer
      第76回日本循環器学会総会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] 血糖値変動が心筋虚血耐性に及ぼす影響について2012

    • Author(s)
      手嶋泰之
    • Organizer
      第59回日本臨床検査医学会
    • Place of Presentation
      京都市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Glucose Fluctuations Aggravate the Vulnerability of the Heart Against Ischemia/reperfusion Injury in Diabetic Rat2012

    • Author(s)
      Yasushi Teshima
    • Organizer
      American Heart Association Scientific Sessions 2012
    • Place of Presentation
      Los Angels
    • Related Report
      2012 Annual Research Report
  • [Presentation] Glucose fluctuations in diabetic rats aggravate cardiac fibrosis resulting in worse outcomes including atrial fibrillation2012

    • Author(s)
      Shotaro Saito
    • Organizer
      第29回国際心臓研究学会(ISHR)日本部会総会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Glucose Fluctuations Aggravate the Vulnerability of Diabetic Heart Against Ischemia/reperfusion mediated via microRNAs modulation2012

    • Author(s)
      Yasushi Teshima
    • Organizer
      9th International Diabetes Federation -Western Pacific Region Congress
    • Place of Presentation
      京都市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Activation of calmodulin kinase II by increased Na^+-H^+ exchange : as a mechanism of high glucose-induced reactive oxygen species production in cardiomyocytes2011

    • Author(s)
      Satoru Nishio, Yasushi Teshima, Tetsunori Saikawa
    • Organizer
      第75回日本循環器学会総会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report
  • [Presentation] 高グルコースによる心筋における活性酸素増加のメカニズムについて2010

    • Author(s)
      西尾諭、手嶋泰之, 他
    • Organizer
      第57回日本臨床検査医学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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