Influence of insulin on cholesterol removal from macrophages and cholesterol ester uptake by HepG2 cells

The fact that an increased blood insulin level is observed in patients with coronary artery disease (CAD) confirms the hypothesis that insulin promotes the development of atherosclerosis. The low high-density lipoprotein (HDL) concentration observed in such patients may contribute to alteration in reverse cholesterol transport and promote the accumulation of sterols in vascular tissue. We examined the effect of insulin (20-1000 mu U mL(-1)) on cholesterol efflux into HDL(3) particles from human blood monocyte/macrophages and rat peritoneal macrophages preloaded with labelled cholesterol esters, and the influence of insulin on the accumulation of sterols by rat liver cells and HepG2 cell fine in vitro models. Insulin at concentrations up to 250 mu U mL(-1) inhibited the efflux of cholesterol from rat macrophages and promoted high uptake of sterols by both types of hepatic cells. Pharmacological concentrations higher than 250 mu U mL(-1) exerted the opposite effect. In the case of human macrophages, an insulin concentration of 20 mu U mL(-1) increased cholesterol removal, whereas 100-200 mu U mL(-1) insulin inhibited cholesterol removal from cells, and very high concentrations (> 350 mu U mL(-1)) again increased cholesterol removal. We have shown that insulin excess counteracts the beneficial effects of HDL in removing cellular cholesterol and, therefore, may promote development of atherogenesis.