Insulin promotes macrophage foam cell formation: Potential implications in diabetes-related atherosclerosis

The prevalence of atherosclerotic cardiovascular disease is higher in patients with type 2 diabetes, a disorder characterized by hyperinsulinemia and insulin resistance. The role of hyperinsulinemia as an independent participant in the atherogenic process has been controversial. In the current study, we tested the effect of insulin and the insulin sensitizer, adiponectin on human macrophage foam cell formation. We found that both insulin and adiponectin increased expression of the type 2 scavenger receptor CD36 by ~2 fold and decreased expression of the ATP-binding cassette transporter ABCA1 by more than 80%. In both cases regulation was post-transcriptional. As a consequence of these changes, we found that oxidized LDL (oxLDL) uptake was increased by 80% and cholesterol efflux to apolipoprotein A1 (apoA1) was decreased by ~25%. This led to 2–3 fold more cholesterol accumulation over a 16 hour period. As reported previously in studies of murine systems, scavenger receptor-A (SR-A) expression on human macrophages was down-regulated by insulin and adiponectin. Insulin and adiponectin did not affect oxLDL induced secretion of monocyte attractant protein-1 (MCP-1) and interleukin-6 (IL-6). These studies suggest that hyperinsulinemia could promote macrophage foam cell formation and thus may contribute to atherosclerosis in patients with type 2 diabetes.