The influence of exendin and GLP-1 on VCAM-1 and ICAM-1 production in endothelium stimulated by TNF-α and glycated albumin

A growing body of evidence indicates that incretins may have pleiotropic beneficial effects beyond lowering glucose blood concentration. The effect of GLP-1 and exendin-4 on coronary arteries endothelium in diabetic and obese individuals has been studied widely. TNF-α is one of adipocytokines. The aim of our study was to evaluate the influence of glycated albumin (GlyAlb; 100; 500 and 1000 mg/L) and pro-inflammatory cytokine, TNF-α (2.5 and 10 ng/mL), on expression of ICAM-1 and VCAM-1 in cultured human endothelial cells derived from coronary arteries. The next goal of the study was to evaluate the influence of GLP-1 (10 nM and 100 nM) and its analogue, exendin-4 (1 nM and 10 nM), on the expression of ICAM-1 and VCAM-1 in these cell line. TNF-α statistically significantly increased VCAM-1 production by endothelial cells, whereas GlyAlb statistically significantly augmented the expression of both tested adhesion molecules. Exendin-4 and GLP-1 statistically significantly reduced the expression of VCAM-1 in endothelial cells stimulated by GlyAlb in dose-dependent manner. When TNF-α was used as the stimulant only exendin-4 in the concentration of 10 nM statistically significantly reduced the expression of VCAM-1. Studied incretins in their both concentrations statistically significantly reduced the expression of ICAM-1 in endothelial cells stimulated by GlyAlb. The influence of TNFα on the expression of ICAM-1 was statistically significantly reduced by both concentrations of exendin-4 but only by the higher concentration of GLP-1. The results of our present study indicate that incretins may present a group of agents developing pleiotropic effects beyond the reduction of blood glucose concentration. Their vasoprotective and cardioprotective action may be of importance in diabetic and obese individuals.