Endocrine Abstracts

Introduction: Liraglutide treatment reduces cardiovascular complications in patients with diabetes mellitus (DM), which may imply a favorable impact on the endothelial function. The aim of the present study was to investigate in vitro the effect of liraglutide on endothelial redox balance and the parallel expression of CRH, UCN1, 2 and 3 neuropeptides, under normoglycemic and hyperglycemic conditions.

Methods: Macroendothelial cell line EAhy926 was incubated for two hours in the presence of hypeglycemic (25 mM) and normoglycemic (5 mM) conditions in the presence of liraglutide (40 nM). Intracellular H₂O₂ levels, eNOS (endothelial nitic oxide synthase) and produced NOx, SOD (superoxide dismutase), catalase and GPx (glutathione peroxidase) activities were determined in cells lysates and culture media, and CRH, UCN1, 2 and 3 gene expression was assessed in total RNA extracts.

Results: Hyperglycemia was accompanied with significant increase of intracellular H₂O₂ and decrease of the studied antioxidant response enzymes (P<0.005). Liraglutide restored the endothelial oxidative balance while it also reduced the activity of the antioxidant enzymes (P<0.005). CRH and UCNs’ expression were further increased (P<0.05) in the presence of liraglutide. Liraglutide did not affect eNOS and SOD activity in normoglycemic conditions, but decreased significantly catalase and GPx activity (P<0.005). CRH and UCNs expression was upregulated in both normoglycemic and hyperglycaemic conditions (P<0.005).

Conclusions: Liraglutide restores the endothelial redox balance of macroendothelial cells which are exposed to high glucose levels and triggers the expression of CRH and UCNs suggesting that part of the antioxidant response is mediated by the CRH family neuropeptides’ expression.