Investigation on molecular mechanism for ischemic cardioprotective effect of endogenous GLP-1 and its clinical significance

• Project/Area Number: 22590775
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Gifu University
• Principal Investigator: HATTORI Arihiro 岐阜大学, 医学部附属病院, 助教 (20542418)
• Co-Investigator(Kenkyū-buntansha): MINATOGUCHI Shinya 岐阜大学, 医学系研究科, 教授 (20190697)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: GLP-1 / 心筋梗塞 / 左室機能障害 / 左心機能 / 心不全 / BNP / 左心駆出率 / miglitol / PI3 kinase / Akt / infarct size / voglibose / eNOS / NO / KATP channel

Research Abstract

In a rabbit model of myocardial infarction with 30 min coronary ischemia and 48 hours of reperfusion, we demonstrated that oral administration of α-glucosidase inhibitors voglibose and miglitol reduced the myocardial infarct size throughproduction of plasma GLP-1, activation of PI3 kinase-Akt-NO pathway and opening of mitochondrial KATP channels. In a clinical study, we demonstrated that plasma GLP- level was significantly increased in patients with impaired cardiac function as compared with those with preserved cardiac function, and that plasma GLP-1 level was inversely correlated with left ventricular ejection fraction. These results suggest that endogenous GLP-1 is a cardioprotective agent for ischemic heart disease and left ventricular dysfunction.

Research Products

• [Journal Article] Both stimulation of GLP-1 receptors and inhibition of glycogenolysis additively contribute to a protective effect of oral miglitol against ischaemia-reperfusion injury in rabbits. (2011)
  • Author(s): Iwasa M, Yamada Y, Kobayashi H, Yasuda S, Kawamura I, Sumi S, Shiraki T, Yamaki T, Ushikoshi H, Hattori A, Aoyama T, Nishigaki K, Takemura G., Fujiwara H, Minatoguchi S.
  • Journal Title: Br J Pharmacol Volume: 164 Pages: 119-131
  • Peer Reviewed
• [Journal Article] Both stimulation of GLP-1 receptors and inhibition of glycogenolysis additively contribute to a protective effect of oral miglitol against ischaemia-reperfusion injury m rabbits (2011)
  • Author(s): Iwasa M, Hattori A, et al
  • Journal Title: Br J Pharmacol Volume: 164 Pages: 119-131
  • Peer Reviewed
• [Journal Article] Anti-diabetic drug voglibose is protective against ischemia-reperfusion injury via GLP-1 receptors and PI3 kinase-Akt-eNOS pathway in rabbits. (2010)
  • Author(s): Iwasa M, Kobayashi H, Yasuda S, Kawamura I, Sumi S, Yamada Y, Shiraki T, Yamaki T, Ushikoshi H, Aoyama T, Nishigaki K, Takemura G, Fujiwara H, Fujiwara T, Minatoguchi S.
  • Journal Title: J Cardiovasc Pharmacol Volume: 55 Pages: 625-34
  • Peer Reviewed
• [Journal Article] Anti-diabetic drug voglibose is protective against ischemia-reperfusion injury via GLP-1 receptors and PI3 kinase-Akt-eNOS pathway in rabbits (2010)
  • Author(s): Iwasa M, Minatoguchi S, et al
  • Journal Title: J Cardiovasc Pharmacol Volume: 55 Pages: 625-634
  • Peer Reviewed
• [Journal Article] Anti-diabetic drug voglibose is protective against ischemia-reperfusion injury via GLP-1 receptors and PI3 kinase-Akt-eNOS pathway in rabbits. (2010)
  • Author(s): Iwasa M, Minatoguchi S, et al.
  • Journal Title: J Cardiovasc Pharmacol Volume: 55 Pages: 625-634
  • Peer Reviewed
• [Journal Article] Elevated plasma GLP-1 levels and enhanced expression of cardiac GLP-1 receptors in patients with left ventricular dysfunction.
  • Author(s): Hattori A, Kawamura I, Yamada Y, Kanamori H, Aoyama T, Ushikoshi H, Kawasaki M, Nishigaki K, Takemura G, Minatoguchi S.
  • Journal Title: BMJ Open Volume: (in press)
  • Peer Reviewed
• [Presentation] Plasma GLP-1 (Glucagon-Like Peptide 1) Level may be Essential Part in Patients with Left Ventricular Dysfunction. (2012)
  • Author(s): 服部有博
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2012-03-16
• [Presentation] Increased Level of Plasma GLP-1 in Patients with Left Ventricular Dysfunction may serve as a Compensatory Mechanism for Cardiac Function. (2012)
  • Author(s): Hattori A, Kawamura I, Yamada Y, Kanamori H, Aoyama T, Kawasaki M, Nishigaki K, Takemura G, Minatoguchi S.
  • Organizer: AHA2012
  • Place of Presentation: Los Angels, USA
• [Presentation] Increased Level of Plasma GLP-1 in Patients with Left Ventricular Dysfunction may serve as a Compensatory Mechanism for Cardiac Function. (2012)
  • Author(s): Arihiro Hattori
  • Organizer: AHA2012
  • Place of Presentation: Los Angeles(USA)