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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

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Abstract

Background and methods

Glucagon Like Peptide-1 (GLP-1), 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.

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Authors and Affiliations

  1. The Hatter Institute and Centre for Cardiology, University College London Hospital & Medical School, Grafton Way, London, WC1E, UK

    Amal K. Bose, Mihaela M. Mocanu & Derek M. Yellon

  2. NovoNordisk A/S, Novo Allé, 2880, Bagsvaerd, Denmark

    Richard D. Carr

Authors
  1. Amal K. Bose
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  2. Mihaela M. Mocanu
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  3. Richard D. Carr
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  4. Derek M. Yellon
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Correspondence to Amal K. Bose.

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Bose, A.K., Mocanu, M.M., Carr, R.D. et al. 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 Drugs Ther 21, 253–256 (2007). https://doi.org/10.1007/s10557-007-6030-6

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  • DOI: https://doi.org/10.1007/s10557-007-6030-6

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