Endocrine Abstracts

Introduction: Diabetes is characterised by increased oxidative stress and an insufficient antioxidant response, which are crucial for the initiation and progression of atherosclerosis. GLP-1 agonists, used for the treatment of diabetes, are considered as cardioprotective agents but under that concept, there are limited data on their ability to influence the endothelial antioxidant response.

Methods: In order to answer this question we studied the influence of liraglutide, a known long-lasting GLP-1 agonist, on the antioxidant response markers (superoxide dismutase (SOD), catalase, glutathione (GSH) system, endothelial nitric oxide synthase (eNOS), intracellular reactive oxygen species (ROS) and extracellular nitric oxide (NOx)) of Eahy926 macroendothelial cells pre-treated in hyperglycemic (25 mM) environment for 2 h.

Results: Hyperglycemia significantly increased the endothelial intracellular ROS content (P<0.001) and decreased eNOS (P<0.05), SOD (P<0.05) and catalase (P<0.001) activity, GSH recycling rate (P<0.001) and Nox levels (P<0.05). Liraglutide (40 nM) restored the increased intracellular ROS to levels comparable to normal glucose treated cells (control). The elimination of intracellular ROS was accomplished by the activation of SOD (P<0.05) and catalase (P<0.001) enzymatic antioxidant response and the increase (P<0.001) of intracellular GSH recycling rate. Moreover, liraglutide restored also eNOS activity and NOx release (P<0.05).

Conclusions: Our results indicate that liraglutide is involved in the redox balance of endothelial cells. Its ability to counterbalance the increased endothelial free radicals induced by hyperglycemia seems to work as a protective mechanism restoring cell function and ameliorating the progression of atherosclerosis process.