Liraglutide

Liraglutide is a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist [1].

GLP-1R, mainly expressed on the pancreatic β cells, is the receptor of glucagon like peptide-1 (GLP-1) which plays an important role in glucose-stimulated insulin release and the preservation of plasma glucose homeostasis. GLP-1R is also expressed on vascular endothelial cells, with potential roles in vascular biology [1].

In human umbilical vein endothelial cell line C11-STH²⁰, liraglutide at 100 nM attenuated induction of plasminogen activator inhibitor type-1 (PAI-1) and vascular adhesion molecule (VAM) expression. In addition, liraglutide also rendered protection against endothelial cell dysfunction, an early abnormality in diabetic vascular disease.

In the ApoE^-/- mouse model, liraglutide (300 μg/kg, b.i.d., s.c.) significantly inhibited GLP-1R-dependent endothelial cell dysfunction. Furthermore, liraglutide treatment also induced endothelial nitric oxide synthase (eNOS) expression while reduced intercellular adhesion molecule-1 (ICAM-1) expression in aortic endothelium. The above effects were again abrogated by the concomitant administration of a GLP-1R antagonist [1].

Reference:

[1]. Gaspari T, Liu H, Welungoda I, et al. A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE^-/- mouse model. Diabetes & Vascular Disease Research, 2011, 8(2): 117-124.