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New Insight into the Cardiac Energy Metabolism in the Pathophysiology of Acute Coronary Syndrome.

Research Project

Project/Area Number 17K09531
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionJikei University School of Medicine

Principal Investigator

Nagoshi Tomohisa  東京慈恵会医科大学, 医学部, 講師 (60408432)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords急性冠症候群 / SGLT / Na利尿ペプチド / インスリン抵抗性 / 虚血再灌流障害 / 共分散構造解析 / ナトリウム利尿ペプチド / 糖代謝 / 共分散構造 / 循環器 / 糖 / 糖尿病
Outline of Final Research Achievements

Glucose becomes an important preferential substrate for metabolism and ATP generation under specific pathological conditions, such as ischemia-reperfusion injury. Using cardiac catheter database, we found that insulin resistance (IR) is precipitously increased during acute coronary syndrome (ACS) attack, while BNP improves IR and promotes glucose utilization only in ACS subjects, but not in non-ACS. Meanwhile, using ex vivo ischemia-reperfusion model with high fat diet mice hearts, we found that cardiac SGLT1, but not SGLT2, plays a compensatory protective role via enhanced glucose utilization, particularly under IR condition, in which stress-induced GLUT4 upregulation is compromised. A series of our recent clinical and basic studies suggests that the acceleration of the glucose metabolism, along with the restoration of insulin sensitivity, is the ideal metabolic therapy for ACS attack.

Academic Significance and Societal Importance of the Research Achievements

IRを主体とした心筋エネルギー代謝障害はACSを含めた重症心不全の病態生理の根幹といえる。虚血急性期病態において、IRを凌駕した心筋糖代謝活性化は心保護的に働く。本研究では、ACS急性期に活性化される神経体液性因子のうち、BNPがカテコラミンと協調して糖利用促進に関わることを示した。心筋糖輸送体に関しては、特に肥満・糖尿病などIR病態下で細胞膜上発現が低下するGLUT4を代償して、SGLT1が虚血心筋への糖供給に重要であることを示した。一方、近年大規模臨床試験で注目された選択的SGLT2阻害薬は、少なくとも短期的な心臓局所への直接作用としては、悪影響を及ぼさないことを確認した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (42 results)

All 2020 2019 2018 2017 2016

All Journal Article (22 results) (of which Peer Reviewed: 16 results,  Open Access: 15 results) Presentation (18 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results) Book (2 results)

  • [Journal Article] Major Influence of Diabetes on Hospitalization for Heart Failure in Patients With Ischemic Heart Diseases2020

    • Author(s)
      Nagoshi Tomohisa
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 3 Pages: 382-383

    • DOI

      10.1253/circj.CJ-20-0015

    • NAID

      130007801795

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2020-02-25
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increase in oxidized low-density lipoprotein level according to hyperglycemia in patients with cardiovascular disease: A study by structure equation modeling2020

    • Author(s)
      Yamada Takayuki、Ogawa Kazuo、Tanaka Toshikazu D.、Nagoshi Tomohisa、Minai Kosuke、Ogawa Takayuki、Kawai Makoto、Yoshimura Michihiro
    • Journal Title

      Diabetes Research and Clinical Practice

      Volume: 161 Pages: 108036-108036

    • DOI

      10.1016/j.diabres.2020.108036

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Highly-sensitized Response of B-type Natriuretic Peptide to Cardiac Ischaemia Quantified by Intracoronary Pressure Measurements2020

    • Author(s)
      Itakura Ryosuke、Inoue Yasunori、Ogawa Kazuo、Nagoshi Tomohisa、Minai Kosuke、Ogawa Takayuki、Kawai Makoto、Yoshimura Michihiro
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 2403-2403

    • DOI

      10.1038/s41598-020-59309-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Collaborative Activities of Noradrenaline and Natriuretic Peptide for Glucose Utilization in Patients with Acute Coronary Syndrome2019

    • Author(s)
      Uno Goki、Nagoshi Tomohisa、Yoshii Akira、Inoue Yasunori、Tanaka Yoshiro、Kimura Haruka、Ito Satoshi、Ogawa Kazuo、Tanaka Toshikazu D.、Minai Kosuke、Ogawa Takayuki、Kawai Makoto、Yoshimura Michihiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 7822-7822

    • DOI

      10.1038/s41598-019-44216-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cardiac ischemia?reperfusion injury under insulin-resistant conditions: SGLT1 but not SGLT2 plays a compensatory protective role in diet-induced obesity2019

    • Author(s)
      Yoshii Akira、Nagoshi Tomohisa、Kashiwagi Yusuke、Kimura Haruka、Tanaka Yoshiro、Oi Yuhei、Ito Keiichi、Yoshino Takuya、Tanaka Toshikazu D.、Yoshimura Michihiro
    • Journal Title

      Cardiovascular Diabetology

      Volume: 18 Issue: 1 Pages: 85-85

    • DOI

      10.1186/s12933-019-0889-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 心不全とアルドステロン2019

    • Author(s)
      名越智古
    • Journal Title

      循環器内科

      Volume: 86 Pages: 133-139

    • Related Report
      2019 Annual Research Report
  • [Journal Article] High Serum Uric Acid is Highly Associated with a Reduced Left Ventricular Ejection Fraction Rather than Increased Plasma B-type Natriuretic Peptide in Patients with Cardiovascular Diseases2019

    • Author(s)
      Oki Yoshitsugu、Kawai Makoto、Minai Kosuke、Ogawa Kazuo、Inoue Yasunori、Morimoto Satoshi、Tanaka Toshikazu、Nagoshi Tomohisa、Ogawa Takayuki、Yoshimura Michihiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41598-018-37053-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between plasma B-type natriuretic peptide and anaemia in heart failure with or without ischaemic heart disease: a retrospective study2019

    • Author(s)
      Tominaga Mitsutoshi、Kawai Makoto、Minai Kosuke、Ogawa Kazuo、Inoue Yasunori、Morimoto Satoshi、Tanaka Toshikazu、Nagoshi Tomohisa、Ogawa Takayuki、Yoshimura Michihiro
    • Journal Title

      BMJ Open

      Volume: 9 Issue: 3 Pages: e024194-e024194

    • DOI

      10.1136/bmjopen-2018-024194

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ミネラルコルチコイド受容体拮抗薬-主要薬剤各論-2019

    • Author(s)
      名越智古
    • Journal Title

      日本臨床

      Volume: 77 Pages: 270-275

    • Related Report
      2018 Research-status Report
  • [Journal Article] 心不全と糖尿病、その総論的な考え方2019

    • Author(s)
      名越智古
    • Journal Title

      循環器内科

      Volume: 85 Pages: 300-305

    • Related Report
      2018 Research-status Report
  • [Journal Article] Nutritional Status Assessment as a Potential Prognostic Indicator in Patients Before the Development of Symptomatic Heart Failure2018

    • Author(s)
      Nagoshi Tomohisa、Yoshimura Michihiro
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 6 Pages: 1501-1502

    • DOI

      10.1253/circj.CJ-18-0454

    • NAID

      130006744331

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2018-05-25
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predictors of oxygenation impairment in medical treatment for type B acute aortic dissection2018

    • Author(s)
      Kashiwagi Yusuke、Komukai Kimiaki、Suzuki Kenichiro、Oi Yuhei、Tominaga Mitsutoshi、Nakata Kotaro、Miyanaga Satoru、Ishikawa Tetsuya、Minai Kosuke、Nagoshi Tomohisa、Yoshimura Michihiro
    • Journal Title

      Heart and Vessels

      Volume: 33 Issue: 12 Pages: 1463-1470

    • DOI

      10.1007/s00380-018-1199-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] レニン-アンジオテンシン-アルドステロン系の新展開2018

    • Author(s)
      名越智古、吉村道博
    • Journal Title

      最新医学

      Volume: 73 Pages: 19-25

    • Related Report
      2018 Research-status Report
  • [Journal Article] インスリン・糖代謝と虚血性心疾患2018

    • Author(s)
      名越智古、吉村道博
    • Journal Title

      循環器内科

      Volume: 84 Pages: 390-397

    • Related Report
      2018 Research-status Report
  • [Journal Article] 心不全の分子機序-アルドステロン2018

    • Author(s)
      名越智古、吉村道博
    • Journal Title

      日本臨床

      Volume: 76 Pages: 123-127

    • Related Report
      2018 Research-status Report
  • [Journal Article] The thermogenic actions of natriuretic peptide in brown adipocytes: The direct measurement of the intracellular temperature using a fluorescent thermoprobe2017

    • Author(s)
      Kimura Haruka、Nagoshi Tomohisa、Yoshii Akira、Kashiwagi Yusuke、Tanaka Yoshiro、Ito Keiichi、Yoshino Takuya、Tanaka Toshikazu D.、Yoshimura Michihiro
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12978-12978

    • DOI

      10.1038/s41598-017-13563-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Close linkage between serum uric acid and cardiac dysfunction in patients with ischemic heart disease according to covariance structure analysis2017

    • Author(s)
      Tanaka Yoshiro、Nagoshi Tomohisa、Kawai Makoto、Uno Goki、Ito Satoshi、Yoshii Akira、Kimura Haruka、Inoue Yasunori、Ogawa Kazuo、Tanaka Toshikazu D.、Minai Kosuke、Ogawa Takayuki、Yoshimura Michihiro
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1

    • DOI

      10.1038/s41598-017-02707-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conflicting relationship between age-dependent disorders, valvular heart disease and coronary artery disease by covariance structure analysis: Possible contribution of natriuretic peptide2017

    • Author(s)
      Fukumoto Risa、Kawai Makoto、Minai Kosuke、Ogawa Kazuo、Yoshida Jun、Inoue Yasunori、Morimoto Satoshi、Tanaka Toshikazu、Nagoshi Tomohisa、Ogawa Takayuki、Yoshimura Michihiro
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 7 Pages: e0181206-e0181206

    • DOI

      10.1371/journal.pone.0181206

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible increase in insulin resistance and concealed glucose-coupled potassium-lowering mechanisms during acute coronary syndrome documented by covariance structure analysis2017

    • Author(s)
      Ito Satoshi、Nagoshi Tomohisa、Minai Kosuke、Kashiwagi Yusuke、Sekiyama Hiroshi、Yoshii Akira、Kimura Haruka、Inoue Yasunori、Ogawa Kazuo、Tanaka Toshikazu D.、Ogawa Takayuki、Kawai Makoto、Yoshimura Michihiro
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 4 Pages: e0176435-e0176435

    • DOI

      10.1371/journal.pone.0176435

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Manifold implications of obesity in ischemic heart disease among Japanese patients according to covariance structure analysis: Low reactivity of B-type natriuretic peptide as an intervening risk factor2017

    • Author(s)
      Tsutsumi Joshi、Minai Kosuke、Kawai Makoto、Ogawa Kazuo、Inoue Yasunori、Morimoto Satoshi、Tanaka Toshikazu、Nagoshi Tomohisa、Ogawa Takayuki、Yoshimura Michihiro
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 5 Pages: e0177327-e0177327

    • DOI

      10.1371/journal.pone.0177327

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Parallel comparison of risk factors between progression of organic stenosis in the coronary arteries and onset of acute coronary syndrome by covariance structure analysis2017

    • Author(s)
      Ogawa Kazuo、Minai Kosuke、Kawai Makoto、Tanaka Toshikazu、Nagoshi Tomohisa、Ogawa Takayuki、Yoshimura Michihiro
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 3 Pages: e0173898-e0173898

    • DOI

      10.1371/journal.pone.0173898

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tissue thrombin is associated with the pathogenesis of dilated cardiomyopathy.2016

    • Author(s)
      Ito K, Hongo K, Date T, Ikegami M, Hano H, Owada M, Morimoto S, Kashiwagi Y, Katoh D, Yoshino T, Yoshii A, Kimura H, Nagoshi T, Kajimura I, Kusakari Y, Akaike T, Minamisawa S, Ogawa K, Minai K, Ogawa T, Kawai M, Yajima J, Matsuo S, Yamane T, Taniguchi I, Morimoto S, Yoshimura M.
    • Journal Title

      Int J Cardiol.

      Volume: 228 Pages: 821-827

    • DOI

      10.1016/j.ijcard.2016.11.176

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Comprehensive Proposals for Glucose Transport Regulation in the Pathophysiology of Cardiovascular Diseases.2019

    • Author(s)
      Tomohisa Nagoshi, Goki Uno, Michihiro Yoshimura
    • Organizer
      The 23rd Annual Scientific Meeting of the Japanese Heart Failure Society.
    • Related Report
      2019 Annual Research Report
  • [Presentation] 虚血性心疾患における糖代謝制御の新知見.2019

    • Author(s)
      名越智古、吉村道博
    • Organizer
      第60回脈管学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] SGLT1 is Essential for Cardioprotection During Ischemia-Reperfusion Injury via Enhanced Glucose Utilization in Diet-induced Obese Mice2019

    • Author(s)
      Akira Yoshii, Nagoshi Tomohisa, Yusuke Kashiwagi, Haruka Kimura, Yoshiro Tanaka, Yuhei Oi, Keiichi Ito, Takuya Yoshino, Toshikazu D Tanaka, MIchihiro Yoshimura
    • Organizer
      American Heart Association-BCVS
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Adipose Tissue Browning Induced by Natriuretic Peptide Exerts Thermogenic Actions and Improves Insulin Resistance in an in vivo Model of Diet-Induced Obese Mice2019

    • Author(s)
      Haruka Kimura, Tomohisa Nagoshi, Akira Yoshii, Yoshiro Tanaka, Yuhei Oi, Michihiro Yoshimura
    • Organizer
      American Heart Association-BCVS
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SGLT1 Plays an Essential Role of Cardioprotection during Ischemia-Reperfusion Injury via Enhanced Glucose Utilization in Diet-induced Obese Mice.2019

    • Author(s)
      吉井顕、名越智古、木村悠、吉村道博
    • Organizer
      日本心脈管作動物質学会 (YIA finalist)
    • Related Report
      2018 Research-status Report
  • [Presentation] In vivo Adipose Tissue Browning Induced by Natriuretic Peptide Activates Thermogenic Actions and Improves Insulin Resistance in Diet-Induced Obese Mice.2019

    • Author(s)
      木村悠、名越智古、吉井顕、吉村道博
    • Organizer
      日本心脈管作動物質学会 (YIA finalist)
    • Related Report
      2018 Research-status Report
  • [Presentation] Comprehensive Proposals for Glucose Transport Regulation in the Pathophysiology of Cardiovascular Diseases.2019

    • Author(s)
      Nagoshi T, Yoshimura M.
    • Organizer
      日本循環器学会学術集会 (Plenary Session)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Thermogenic action of B-type natriuretic peptide in patients with cardiovascular diseases according to covariance structure analysis.2018

    • Author(s)
      Kang R, Nagoshi T, Kimura H, Tanaka TD, Yoshii A, Ogawa K, Minai K, Ogawa T, Kawai M, Yoshimura M
    • Organizer
      European Society of Cardiology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] SGLT1 exhibits ischemic tolerance and contributes to cardioprotection during ischemia-reperfusion injury in diet-induced obese mice.2018

    • Author(s)
      Yoshii A, Nagoshi T, Yoshimura M.
    • Organizer
      日本心不全学会 (YIA finalist)
    • Related Report
      2018 Research-status Report
  • [Presentation] Thermogenic action of B-type natriuretic peptide in patients with cardiovascular diseases according to covariance structure analysis.2018

    • Author(s)
      Kang R, Nagoshi T, Yoshimura M.
    • Organizer
      日本心不全学会 (YIA finalist)
    • Related Report
      2018 Research-status Report
  • [Presentation] “代謝病”-心不全の克服を目指して2018

    • Author(s)
      名越智古
    • Organizer
      日本心不全学会 (Symposium)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] A SGLT2-inhibitor Does Not Exert a Baleful Influence on the Heart during Ischemia-Reperfusion Injury.2018

    • Author(s)
      Yoshii A, Nagoshi T, Kashiwagi Y. Kimura H. Tanaka Y. Ito K. Yoshino T, Tanaka T. and Yoshimura M.
    • Organizer
      Japanese Circulation Society-BCVR
    • Related Report
      2017 Research-status Report
  • [Presentation] The Thermogenic Effects of Natriuretic Peptide on Brown Adipocytes in a Low Temperature-Sensitive Manner.2018

    • Author(s)
      Kimura H., Nagoshi T, Yoshii A, Kashiwagi Y. Tanaka Y. Ito K. Yoshino T, Tanaka T. and Yoshimura M.
    • Organizer
      Japanese Circulation Society-BCVR (Poster Award)
    • Related Report
      2017 Research-status Report
  • [Presentation] Natriuretic Peptide Exerts Thermogenic Effects on Brown Adipocytes in a Low-Temperature-Sensitive Manner: Direct Measurement of Intracellular Temperature Using Fluorescent Thermoprobe2018

    • Author(s)
      Kimura H., Nagoshi T, Yoshii A, Kashiwagi Y. Tanaka Y. Ito K. Yoshino T, Tanaka T. and Yoshimura M.
    • Organizer
      Japanese Circulation Society
    • Related Report
      2017 Research-status Report
  • [Presentation] No Harmful Effects of a Selective SGLT2-inhibitor in contrast to Impairment of Cardiac Energy Metabolism by Phlorizin during Ischemia-Reperfusion Injury in Mice.2017

    • Author(s)
      Yoshii A, Nagoshi T, Kashiwagi Y. Kimura H. Tanaka Y. Ito K. Yoshino T, Tanaka T. and Yoshimura M.
    • Organizer
      American Heart Association
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The Thermogenic Actions of Natriuretic Peptide in Brown Adipocytes: The Direct Measurement of the Intracellular Temperature Using a Fluorescent Thermoprobe.2017

    • Author(s)
      Kimura H., Nagoshi T, Yoshii A, Kashiwagi Y. Tanaka Y. Ito K. Yoshino T, Tanaka T. and Yoshimura M.
    • Organizer
      American Heart Association
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 褐色脂肪細胞におけるANPの熱産生効果と作用機序:蛍光プローブを用いた細胞内温度測定による検討2017

    • Author(s)
      木村悠,名越智古,吉井顕,田中祥朗,吉村道博
    • Organizer
      日本心血管内分泌代謝学会総会 (YIA finalist)
    • Related Report
      2017 Research-status Report
  • [Presentation] No Negative Impact of a Selective SGLT2-inhibitor as Contrasted with Phlorizin-induced Cardiac Energy Metabolism Disturbance during Ischemia-Reperfusion Injury in Mice2017

    • Author(s)
      Yoshii A, Nagoshi T, Yoshimura M
    • Organizer
      International Society for Heart Research (Featured Research Session)
    • Related Report
      2017 Research-status Report
  • [Book] 循環器疾患 最新の治療 2020-20212020

    • Author(s)
      名越智古、吉村道博
    • Total Pages
      500
    • Publisher
      南江堂
    • ISBN
      9784524249763
    • Related Report
      2019 Annual Research Report
  • [Book] 実験医学別冊2020

    • Author(s)
      名越智古
    • Total Pages
      204
    • Publisher
      羊土社
    • ISBN
      9784758122085
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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