Bose, AK; Mocanu, MM; Carr, RD; Yellon, DM; (2007) Myocardial ischaemia-reperfusion injury is attenuated by intact glucagon like peptide-1 (GLP-1) in the in vitro rat heart and may involve the p70s6K pathway. CARDIOVASC DRUG THER , 21 (4) 253 - 256. 10.1007/s10557-007-6030-6.
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Background and methods Glucagon Like Peptide-1 (GLP1), one of the most potent incretin hormones, has potential beneficial actions on the ischaemic and failing heart. This study sought to further identify the mechanisms of action of GLP-1 on the ischaemic heart using an in vitro isolated perfused rat heart model of ischaemic-reperfusion injury ( measuring infarct size to area of risk (%)) subjected to 35 min regional ischaemia and 2 h reperfusion. To examine the effect of intact GLP-1 we used an inhibitor of GLP-1 breakdown, Valine pyrrolidide (VP). The downstream target of phosphatidylinositol 3-kinase includes the mTOR/p70s6 kinase pathway which was pharmacologically inhibited by rapamycin.Results and conclusion GLP-1 alone did not decrease myocardial infarction (54.4 +/- 3.1%). VP alone did not decrease myocardial infarction ( 52.5 +/- 4%). GLP- 1 in the presence of VP produced significant reduction in myocardial infarction compared to control hearts ( 28.4 +/- 2.7% vs. 56.4 +/- 3.9% vs. P< 0.05). Inhibiting p70s6 Kinase with rapamycin completely abolished GLP- 1 induced protection ( 57.1 +/- 4.9% vs. 28.4 +/- 2.7% P< 0.05). There was no detectable increase in the phosphorylated p70s6k after either 5 or 10 min of treatment with GLP-1/VP or with VP alone in comparison to control blots. In conclusion we show for the first time that the protective effects of GLP-1 are mediated by intact GLP-1 and can be inhibited by blocking the p70s6 kinase.
|Title:||Myocardial ischaemia-reperfusion injury is attenuated by intact glucagon like peptide-1 (GLP-1) in the in vitro rat heart and may involve the p70s6K pathway|
|Keywords:||glucagon like peptide-1, ischaemic preconditioning, rapamycin, reperfusion injury, CELL-SURVIVAL|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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