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Effect of insulin on platelet aggregation in coronary artery bypass grafting

Research Project

Project/Area Number 17K10771
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular surgery
Research InstitutionKyushu University of Health and Welfare

Principal Investigator

Yamamoto Ryuichi  九州保健福祉大学, 薬学部, 教授 (10094111)

Co-Investigator(Kenkyū-buntansha) 蒲生 修治  九州保健福祉大学, 薬学部, 教授 (20273930)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords冠動脈バイパス手術 / 糖尿病 / 血小板 / インスリン / 伏在静脈 / スパズム / セロトニン(5-HT) / セロトニン / 血小板凝集 / 心バイパス手術
Outline of Final Research Achievements

It is likely that the increased contractile response to serotonin (5-HT) found in the blood vessels of diabetic patients may be due to the relative increase in the number of 5-HT2A receptors in the vascular smooth muscle cell membrane by the deficiency of insulin. The inhibitory effect of insulin on platelet aggregation induced by 5-HT was confirmed in rabbit platelets. However, in human platelets, the inhibitory effect of insulin on platelet aggregation induced by 5-HT was not confirmed. Platelet aggregation by 5-HT stimulation was observed after collagen stimulation, and its action was confirmed to be much smaller than that of ADP, which is another platelet-derived substance. Therefore, it is likely that the enhanced vasoconstrictor responsiveness to 5-HT observed in the blood vessels of diabetic patients is limited to vasoconstrictor muscle cells, and the contribution of 5-HT alone stimulation to platelets is small.

Academic Significance and Societal Importance of the Research Achievements

我々はこれまで、糖尿病におけるグラフト血管れん縮の増大には、インスリンによる細胞膜からの5-HT2A受容体インターナリゼーション作用の減弱が関連することを明らかにしてきた。しかし、この反応が血小板でも同様に起こるかは分かっていない。現在、周術期の血管れん縮抑制にはCa拮抗薬やアンジオテンシンⅡ受容体拮抗薬等が使用され、治療成績は改善されつつあるが、より有効で安全な予防法の確立が必要とされている。食生活の変化や高齢化社会の進展などにより、糖尿病患者に対する冠動脈バイパス手術施行回数が年々増加する中で、本研究の社会的意義は大きいと思われる。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2022 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Brazilian propolis (AF-08) inhibits collagen-induced platelet aggregation without affecting blood coagulation2021

    • Author(s)
      Chihiro Sugita, Atsushi Yamashita, Shigetoshi Tsutsumi, Hisahiro Kai, Tohru Sonoda, Hiroki Yoshida, Ryuichi Yamamoto, Yujiro Asada, Masahiko Kurokawa.
    • Journal Title

      Journal of natural medicines.

      Volume: 75 Issue: 4 Pages: 975-984

    • DOI

      10.1007/s11418-021-01518-w

    • NAID

      40022681000

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of M-1, a Major Metabolite of Sarpogrelate, on 5-HT-Induced Constriction of Isolated Human Internal Thoracic Artery2020

    • Author(s)
      Naoko Tanaka-Totoribe, Muneaki Hidaka, Shuji Gamoh, Atsuko Yokota, Eisaku Nakamura, Masachika Kuwabara, Jun Tsunezumi, Ryuichi Yamamoto
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 12 Pages: 1979-1982

    • DOI

      10.1248/bpb.b20-00591

    • NAID

      130007948737

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-12-01
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differences in the response to periarterial nerve stimulation or exogenous noradrenaline infusion in the mesenteric vascular bed with the intestinal tract harvested from commonly used rat models of hypertension2019

    • Author(s)
      Gamoh S, Shiba T, DiPette DJ, Yamamoto R.
    • Journal Title

      Clinical and Experimental Pharmacology and Physiology

      Volume: 46 Issue: 5 Pages: 427-434

    • DOI

      10.1111/1440-1681.13068

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diabetes Mellitus Induces Hyperreactivity of 5-Hydroxytryptamine (5-HT)-Induced Constriction in Human Internal Thoracic Artery and Is Associated with Increase in the Membrane Protein Level of 5-HT<sub>2A</sub> Receptor2018

    • Author(s)
      Shiba T., Yokota A., Gamoh S., Tanaka-Totoribe N., Kuwabara M., Nakamura E., Hayase T, Nakamura K., Yamamoto R.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 5 Pages: 820-823

    • DOI

      10.1248/bpb.b17-01000

    • NAID

      130006730769

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-05-01
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト冠動脈バイパス内胸動脈グラフトのれん縮を予防するパパベリンの至適濃度について2022

    • Author(s)
      鳥取部直子,蒲生修治,横田敦子,中村栄作,桑原正知, 常住淳, 山本隆一
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 冠動脈バイパス手術(CABG)における内胸動脈バイパスグラフトの血管れん縮を予防するパパベリンの至適濃度の検討2020

    • Author(s)
      鳥取部直子、蒲生修治、日高宗明、比佐博彰、山本隆一
    • Organizer
      日本薬学会141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] ブラジル産プロポリス(AF-08)と成分フラボノイドの血栓症に対する有効性評価 ―血小板凝集と血液凝固に対する抑制作用の検討―2020

    • Author(s)
      杉田千泰,山下篤,堤重敏,吉田裕樹,山本隆一,浅田祐士郎,黒川昌彦
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Naloxone, an antagonist of alpha receptors, significantly inhibits extra-junctional alpha-1 receptor-mediated response, but not intra-junctional alpha-1 receptor mediated response, in rat isolated perfused intestinal vasculatures2020

    • Author(s)
      鳥取部直子、蒲生修治、日高宗明、比佐博彰、山本隆一
    • Organizer
      日本薬学会140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 慢性動脈閉塞症治療薬 サルポグレラート(選択的5-HT2受容体拮抗薬)の主要代謝産物 M-1の血管収縮抑制効果2019

    • Author(s)
      )芝 達雄, 鳥取部直子, 蒲生修治, 横田敦子, 中村栄作, 桑原正知, 比佐博彰, 山本隆一
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] In patients with diabetes mellitus(DM), but not in patients without DM, angiotensin II is a vasospasm inducer in both venous and arterial conduits under coronary artery bypass grafting2018

    • Author(s)
      Tatsuo Shiba, Atsuko Yokota, Shuji Gamoh, Naoko Tanaka-Totoribe, Masachika Kuwabara, Eisaku Nakamura, Takairo Hayase, Kunihide Nakamura, Hiroaki Hisa, Ryuichi Yamamto
    • Organizer
      18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY(国際学会)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 下肢静脈瘤の進展メカニズム -血管内径と収縮力の関係-2018

    • Author(s)
      鳥取部直子, 芝達雄, 蒲生修治, 横田敦子, 中村栄作, 桑原正知, 比佐博彰, 山本隆一
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] フラボンに分類されるフラボノイドの血小板および血液凝固系に対する影響2018

    • Author(s)
      杉田千泰, 中馬祥子, 吉田桂二郎, 山下篤, 吉田裕樹, 渡辺渡, 山本隆一, 黒川昌彦
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2023-01-30  

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