Is diabetes mellitus (DM) a high risk factor for coronary artery bypass grafting?

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591556
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kyushu 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): GAMOH Shuji 九州保健福祉大学, 薬学部, 講師 (20273930) ; KANAI Tasuku 九州保健福祉大学, 薬学部, 助教 (20551295) ; MATSUO Yasuko 九州保健福祉大学, 薬学部, 助手 (30551296)
• Project Period (FY): 2010 – 2012
• Keywords: 心バイパス手術 / バイパスグラフト / れん縮 / セロトニン / ヒト伏在静脈

Research Abstract

The aim of this study is to determine whether diabetes mellitus (DM) is a high risk factor for coronary artery bypass grafting (CABG). In isolated human endothelium-denuded saphenous vein (SV), the constrictions caused by 5-hydroxytryptamine (5-HT) were significantly greater (hyperreactivity) in the DM patients than in the non-DM (NDM) patients. In the study, we demonstrated that the hyperreactivity to 5-HT in the SV smooth muscle of DM patients resulted from not only the enhanced phosphorylation of myosin light chain phosphatase (MLCP) but also the defective protein levels of MLCP. Furthermore, we demonstrated that the relaxant effect of insulin on 5-HT-induced constriction of SV is mediated in part by the internalization of plasma membrane 5-HT2A receptors and the production of nitric oxide via the PI3-K/Akt pathway. In conclusion,we demonstrated that DM is a high risk factor for CABG.

Research Products

• [Journal Article] Insulin induces internalization of the plasma membrane 5-hydroxytryptamine 2A (5-HT2A) receptor in the isolated human endothelium-denuded saphenous vein via the phosphatidylinositol 3-kinase pathway. (2012)
  • Author(s): Kanai T., Kuwabara M., Tanaka-Totoribe N., Nakamura E., Matsuo Y., Gamoh S.,Suzuki A., Asada Y., Hisa H., YamamotoR.
  • Journal Title: Journal of Pharmacological Sciences Volume: 118 (2) Pages: 178-185
  • DOI: doi: 10.1254/phs.1172FP
  • Peer Reviewed
• [Journal Article] The defective protein level of myosin light chain phosphatase (MLCP) in the isolated saphenous vein, as a vascular conduit in coronary artery bypass grafting (CABG), harvested from patients with diabetes mellitus (DM). (2011)
  • Author(s): Matsuo Y., Kuwabara M.,Tanaka-Totoribe N., Kanai T., NakamuraE., Gamoh S., Suzuki A., Asada Y., Hisa H., Yamamoto R.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 412 (2) Pages: 323-327
  • DOI: doi:10.1016/j.bbrc.011.07.097
  • Peer Reviewed
• [Journal Article] Relative contributions of 5-hydroxytryptamine (5-HT) receptor subtypes in 5-HT-induced vasoconstriction of the distended human saphenous vein as a coronary artery bypass graft. (2011)
  • Author(s): Nakamura E., Tanaka N., Kuwabara M.,Yamashita A., Matsuo Y., Kanai T.,Asada Y., Hisa H., Yamamoto R.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 34 (1) Pages: 82-86
  • DOI: doi: 10.1248/bpb.34.82
  • Peer Reviewed
• [Presentation] 摘出ヒト内皮除去伏在静脈でのインスリンによる細胞膜セロトニン2A受容体のインターナリゼーション促進効果 (2012)
  • Author(s): 中村栄作、児嶋一司、新名克彦、横田敦子、金井祐、桑原正知、蒲生修治、比佐博彰、山本隆一、浅田祐士郎
  • Organizer: 第65回日本胸部外科学会総会
  • Place of Presentation: 福岡
  • Year and Date: 20121000
• [Presentation] インスリンはヒト内皮除去摘出大伏在静脈において細胞膜セロトニン2A受容体のインターナリゼーションを引き起こす (2012)
  • Author(s): 金井祐、桑原正知、鳥取部直子、松尾徳子、中村栄作、蒲生修治、鈴木彰人、浅田祐士郎、比佐博彰、山本隆一
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 20120300
• [Presentation] 糖尿病患者の大伏在静脈におけるMLCPタンパクレベルの低下 (2012)
  • Author(s): 松尾徳子、桑原正知、鳥取部直子、金井祐、中村栄作、蒲生修治、鈴木彰人、浅田祐士郎、比佐博彰、山本隆一
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 20120300
• [Presentation] PI3K経路を介したヒト大伏在静脈におけるインスリンの血管弛緩反応 (2011)
  • Author(s): 金井祐、桑原正知、中村栄作、鳥取部直子、松尾徳子、比佐博彰、山本隆一
  • Organizer: 第28回日本薬理学会九州支部会
  • Place of Presentation: 福岡
  • Year and Date: 20111200
• [Presentation] 糖尿病患者の大伏在静脈におけるセロトニン誘発性血管反応増大メカニズムの検討 (2011)
  • Author(s): 松尾徳子、桑原正知、鳥取部直子、金井祐、中村栄作、蒲生修治、浅田祐士郎、比佐博彰、山本隆一
  • Organizer: 第64回日本薬理学会西南部会
  • Place of Presentation: 福岡
  • Year and Date: 20111100
• [Presentation] ヒト内皮除去大伏在静脈におけるインスリンのNO非依存性血管弛緩反応 (2011)
  • Author(s): 金井祐、松尾徳子田中直子、桑原正知、比佐博彰、山本隆一
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20110300
• [Presentation] セロトニンの血管収縮反応に対するインスリンの抑制効果-摘出ヒト大伏在静脈での検討- (2010)
  • Author(s): 金井祐、松尾徳子、田中直子、桑原正知、比佐博彰、山本隆一
  • Organizer: 第63回日本薬理学会西南部会
  • Place of Presentation: 鹿児島
  • Year and Date: 20101100
• [Presentation] Different contributions of Rho-kinase to the vasoconstrictions caused by5-HT and noradrenalin in the isolated internal thoracic artery and saphenousvein. (2010)
  • Author(s): Tanaka N., Kanai T., Matsuo Y.,Kuwabara M., Nakamura E., Nakamura K., Asada Y., Hisa H., Yamamoto R.
  • Organizer: World Pharma 2010・copenhagen,Denmark・
  • Place of Presentation: デンマーク、コペンハーゲン
  • Year and Date: 20100700