Signalling pathways activated by glucagon-like peptide-1 (7-36) amide in the rat heart and their role in protection against ischaemia
| dc.contributor.author | Huisamen, Barbara | |
| dc.contributor.author | Genade, Sonia | |
| dc.contributor.author | Lochner, Amanda | |
| dc.date.accessioned | 2012-01-24T09:55:52Z | |
| dc.date.available | 2012-01-24T09:55:52Z | |
| dc.date.issued | 2008-04 | |
| dc.description | The original publication is available at http://www.cvja.co.za/ | en_ZA |
| dc.description.abstract | Glucagon-like peptide-1 is an incretin hormone proposed to have insulinomimetic effects on peripheral insulin-sensitive tissue. We examined these effects on the heart by using isolated, perfused rat hearts and adult ventricular myocytes. During normoxic perfusion, no effects of escalating concentrations of GLP-1 on either heart rate or left ventricular developed pressure were found. With functional performance as readout, we found that GLP-1 directly protected the heart against damage incurred by global low-flow ischaemia. This protection was sensitive to the presence of iodo-acetate, implicating activation of glycolysis, and was abolished by wortmannin, indicative of PI-3-kinase as mediator of protection. I n addition, GLP-1 had an infarct-sparing effect when supported by the presence of the dipeptidyl peptidase-IV inhibitor valine pyrrolidide. GLP-1 could not directly activate protein kinase B (also called Akt) or the extracellular regulated kinases Erk1/2 in hearts or cardiocytes under normoxic conditions, but phosphorylation of the AMP-activated kinase (AMPK) on Thr172 was enhanced. I n addition, the glycolytic enzyme phosphofructokinase- 2 was activated dose dependently. During reperfusion after ischaemia, modulation of the phosphorylation of PKB/Akt as well as AMPK was evident. GLP-1 therefore directly protected the heart against low-flow ischaemia by enhancing glycolysis, probably via activation of AMP kinase and by modulating the profile of activation of the survival kinase PKB/Akt. | en_ZA |
| dc.description.version | Publisher's version | en_ZA |
| dc.format.extent | pp. 77-81 : ill. | |
| dc.identifier.citation | Huisamen, B., Genade, S. & Lochner, A. 2008. Signalling pathways activated by glucagon-like peptide-1 (7-36) amide in the rat heart and their role in protection against ischaemia. Cardiovascular Journal of Africa, 19(2), 77-83. | en_ZA |
| dc.identifier.issn | 1680-0745 (online) | |
| dc.identifier.issn | 1995-1892 (print) | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/19366 | |
| dc.language.iso | en_ZA | |
| dc.publisher | Clinics Cardiv Publishing | en_ZA |
| dc.rights.holder | Cardiovascular Journal of Africa holds the copyright | en_ZA |
| dc.subject | Peptide-1 | en_ZA |
| dc.subject | Ischaemia | en_ZA |
| dc.subject | Kinase Akt | en_ZA |
| dc.title | Signalling pathways activated by glucagon-like peptide-1 (7-36) amide in the rat heart and their role in protection against ischaemia | en_ZA |
| dc.type | Article | en_ZA |