Liraglutide

Liraglutide attenuates induction of plasminogen activator inhibitor type-1 (PAI-1) and vascular adhesion molecule (VAM) expression in human vascular endothelial cells (hVECs) in vitro and may afford protection against endothelial cell dysfunction (ECD), an early abnormality in diabetic vascular disease. In vitro studies demonstrates GLP-1R-dependent this compound-mediated inhibition of stimulated PAI-1 and VAM expression[3].

In vivo studies of vascular reactivity and immunohistochemical analysis are performed in the ApoE-/- mouse model. They demonstrate significant improvement in endothelial function in liraglutide treated mice, a GLP-1R dependent effect. This compound treatment also increases endothelial nitric oxide synthase (eNOS) and reduces intercellular adhesion molecule-1 (ICAM-1) expression in aortic endothelium, an effect again dependent on the GLP-1R[3]. It reduces hyperglycemia in T2D mouse models by increasing pancreatic b cell mass through enhanced proliferation[2].

• Cell lines

  human umbilical vein endothelial cell line C11-STH20

• Concentrations

  100 nM

• Incubation Time

  16 h

• Method

  C11-STH cells are cultured to confluence at 37°C in gelatin-coated Nunclon cell culture dishes in Media-199 supplemented with penicillin/streptomycin, 20% FCS, 20 µg/ml endothelial cell growth factor and 20 µg/ml heparin. C11-STH cells are incubated under serum free conditions with liraglutide (100 nM) or the GLP-1 receptor antagonist exendin (9-39) (100 nM) alone or with 10 ng/ml TNFα for 16 h alone or in combination with this compound and/or exendin (9-39). ELISA assays for VCAM-1 and ICAM-1 are performed using conditioned medium from C11-STH cells to determine protein expression levels.

• Animal Models

  Athymic nude mice

• Dosages

  300 μg/kg/day

• Administration

  s.c.