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Pichi, A., Gao, X., Belmadani, S., Potter, B.J., Focardi M., Chilian, W.M. and Zhang, C. (2006) Tumor necrosis fac- tor-a induces endothelial dysfunction in the prediabetic metabolic syndrome. Circulation Research, 99, 69-77. doi:10.1161/01.RES.0000229685.37402.80

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

  AUTHORS: Krzysztof Siemianowicz, Tomasz Francuz, Wojciech Garczorz

  KEYWORDS: Incretins; Endothelium; Adhesion Molecules

  JOURNAL NAME: Health, Vol.4 No.12A, December 31, 2012

  ABSTRACT: 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-a 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 proinflammatory 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-a statistically significantly increased VCAM-1 production by endothelial cells, whereas GlyAlb statistically significantly augmented the expression of both tested adhesion mole- cules. Exendin-4 and GLP-1 statistically significantly reduced the expression of VCAM-1 in endothelial cells stimulated by GlyAlb in dose-de- pendent manner. When TNF-a 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 TNF- a 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 vaso-protective and cardioprotective action may be of importance in diabetic and obese individuals.