Insulin potentiates cytokine-induced VCAM-1 expression in human endothelial cells

Hyperinsulinemia is an independent risk factor for cardiovascular events and may contribute to cardiovascular disease. Low-grade chronic inflammation has been implicated in the pathogenesis of atherosclerosis. We aimed at determining the impact of pathophysiologically high insulin concentrations on cytokine-induced endothelial activation in human umbilical vein endothelial cells (HUVEC). HUVEC were incubated with insulin (0–24 h) ± tumor necrosis factor (TNF)-α or lipopolysaccharide (LPS). At pathophysiological/pharmacological concentrations (10− 9–10− 7 mol/L), insulin selectively induced VCAM-1 expression and potentiated the effects of TNF-α and LPS, effects reverted by the proteasome inhibitor lactacystin. Compared with TNF-α alone, insulin + TNF-α doubled U937 cell adhesion. Insulin markedly increased TNF-α-induced NF-κB activation and induced phosphorylated IκB-α accumulation. Therefore, hyperinsulinemia enhances cytokine-induced VCAM-1 expression in endothelial cells, thus potentially contributing to detrimental effects of other inflammatory stimuli on atherogenesis.