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Study of the inhibitory effect of GLP-1 preparation on coronary artery bypass graft vasospasm in patients with diabetes mellitus

Research Project

Project/Area Number 16K10646
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

GAMOH Shuji  九州保健福祉大学, 薬学部, 准教授 (20273930)

Co-Investigator(Kenkyū-buntansha) 山本 隆一  九州保健福祉大学, 薬学部, 教授 (10094111)
芝 達雄  九州保健福祉大学, 薬学部, 助教 (00634958)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
KeywordsCABG / vasospasm / diabetes mellius / serotonin / angiotensin-II / membrane receptor / 冠動脈バイパス術 / グラフトれん縮 / 糖尿病 / GLP-1アナログ / セロトニン / 大伏在静脈 / 内胸動脈 / アンジオテンシンⅡ / 冠動脈バイパス手術 / 血管攣縮 / インクレチン製剤 / GLP-1アナログ製剤 / バイパスグラフト / 薬理学 / 細胞膜受容体 / シグナル伝達
Outline of Final Research Achievements

Bypass grafts harvested from Diabetes mellitus (DM) tends to contraction causing to spasm after implantation. In this study, we investigated the effect of Exendin-4, one of the GLP-1 analogues used as a treatment for DM, on serotonin-induced vasoconstriction in human saphenous vein. Pretreatment with Exendin-4 significantly suppressed 5-HT-induced vasoconstriction in human saphenous vein. Moreover, SQ225361, an inhibitor of adenylate cyclase, diminished the suppressing effect of Exendin-4. These results suggest that Exendin-4 may suppress vasospasm in human saphenous vein, used as bypass graft, via activation of adenylate cyclase.

Academic Significance and Societal Importance of the Research Achievements

糖尿病患者は、冠動脈バイパス手術の予後が不良となりやすいことが知られるが、その有効な解決策はいまだ見出されていない。一方、糖尿病患者では非糖尿病患者よりも冠動脈バイパス手術が適応となる重症の動脈硬化をきたしやすい。本研究の結果は、糖尿病の治療薬としてGLP-1製剤を使用することにより、バイパス手術において移植血管のスパズムを抑制できる可能性を示唆していることから、本研究をさらに発展させることにより、糖尿病患者に対するバイパス手術の成功率を上げ、予後を改善する方法の開発につながる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2020 2019 2018 2017 2016

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [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-HT2A Receptor.2018

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

      Biol Pharm Bull

      Volume: 41 Pages: 820-823

    • NAID

      130006730769

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiotensin II, as well as 5-hydroxytriptamine, is a potent vasospasm inducer of saphenous vein graft for coronary artery bypass grafting in patients with diabetes mellitus.2016

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

      Biochemistry and Biophysics Reports

      Volume: 6 Pages: 82-87

    • DOI

      10.1016/j.bbrep.2016.03.008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ラット摘出腸管血管灌流標本において、麻薬拮抗薬であるナロキソンは血管平滑筋 extrajunctional α1 受容体を抑制するが intrajunctional α1 受容体には作用しない2020

    • Author(s)
      鳥取部 直子, 蒲生 修治, 日髙 宗明, 比佐 博彰, 山本 隆一
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research 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)
      1)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 grafting.2018

    • Author(s)
      Tatsuo Shiba, Atsuko Yokota, Shuji Gamoh, Naoko Tanaka-Totoribe, Masachika Kuwabara, Eisaku Nakamura, Takahiro Hayase, Kunihide Nakamura, Hiroaki Hisa, Ryuichi Yamamoto
    • Organizer
      18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY
    • 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)
      1)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] ヒト内胸動脈および伏在静脈におけるアンギオテンシンⅡ誘発性収縮反応に対する糖尿病の影響2017

    • Author(s)
      芝達雄, 蒲生修治, 鳥取部直子, 横田敦子, 桑原正知, 比佐博彰, 山本隆一
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト伏在静脈および内胸動脈におけるセロトニン誘発性収縮に対する糖尿病の影響2017

    • Author(s)
      芝達雄, 蒲生修治, 鳥取部直子, 横田敦子, 桑原正知, 比佐博彰, 山本隆一
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 糖尿病患者におけるアンギオテンシンII誘発性血管収縮反応増強メカニズムについて-摘出ヒト大伏在静脈での検討-2016

    • Author(s)
      横田敦子, 新名克彦, 早瀬崇洋, 芝達雄, 鳥取部直子, 蒲生修治, 桑原正知, 山本隆一
    • Organizer
      第69回日本胸部外科学会定期学術集会
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2016-09-28
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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