Signalling pathways activated by glucagon-like peptide-1 (7-36) amide in the rat heart and their role in protection against ischaemia
Date
2008-04
Authors
Huisamen, Barbara
Genade, Sonia
Lochner, Amanda
Journal Title
Journal ISSN
Volume Title
Publisher
Clinics Cardiv Publishing
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.
Description
The original publication is available at http://www.cvja.co.za/
Keywords
Peptide-1, Ischaemia, Kinase Akt
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.