Bose, AK; Mocanu, MM; Carr, RD; Brand, CL; Yellon, DM; (2005) Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. DIABETES , 54 (1) 146 - 151.
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Glucagon-like peptide 1 (GLP-1), a gut incretin hormone that stimulates insulin secretion, also activates antiapoptotic signaling pathways such as phosphoinositide 3-kinase and mitogen-activated protein kinase in pancreatic and insulinoma cells. Since these kinases have been shown to protect against myocardial injury, we hypothesized that GLP-1 could directly protect the heart against such injury via these prosurvival signaling pathways. Both isolated perfused rat heart and whole animal models of ischemia/reperfusion were used, with infarct size measured as the end point of injury. In both studies, GLP-1 added before ischemia demonstrated a significant reduction in infarction compared with the valine pyrrolidide (an inhibitor of its breakdown) or saline groups. This protection was abolished in the in vitro hearts by the GLP-1 receptor antagonist exendin (9-39), the cAMP inhibitor Rp-cAMP, the PI3kinase inhibitor LY294002, and the p42/44 mitogen-activated protein kinase inhibitor UO126. Western blot analysis demonstrated the phosphorylation of the proapoptotic peptide BAD in the GLP-1-treated groups. We show for the first time that GLP-1 protects against myocardial infarction in the isolated and intact rat heart. This protection appears to involve activating multiple prosurvival kinases. This finding may represent a new therapeutic potential for this class of drug currently undergoing clinical trials in the treatment of type 2 diabetes.
|Title:||Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury|
|Keywords:||ARTERIAL-BLOOD-PRESSURE, ACUTE MYOCARDIAL-INFARCTION, ANESTHETIZED PIG, CELL APOPTOSIS, BETA-CELLS, KINASE-C, INSULIN, CAMP, RECEPTOR, INHIBITION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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