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

Hyperinsulinemia is an independent risk factor for cardiovascular events and may contribute to cardio-
vascular 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)-? 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-? andLPS, effects reverted by the proteasome inhibitor lactacystin. Compared
with TNF-? alone, insulin+TNF-? doubled U937 cell adhesion. Insulin markedly increased TNF-?-induced
NF-?B activation and induced phosphorylated I?B-? accumulation. Therefore, hyperinsulinemia enhances
cytokine-induced VCAM-1 expression in endothelial cells, thus potentially contributing to detrimental effects
of other inflammatory stimuli on atherogenesis.