Insulin promotes macrophage foam cell formation: potential implications in diabetes-related atherosclerosis. Lab Invest 2012 Aug;92(8):1171-80
Date
04/25/2012Pubmed ID
22525426Pubmed Central ID
PMC3407326DOI
10.1038/labinvest.2012.74Scopus ID
2-s2.0-84864481830 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
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 the expression of the type 2 scavenger receptor CD36 by approximately twofold and decreased the expression of the ATP-binding cassette transporter ABCA1 by >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 two- to threefold more cholesterol accumulation over a 16-h period. As reported previously in studies of murine systems, scavenger receptor-A (SR-A) expression on human macrophages was downregulated 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.
Author List
Park YM, R Kashyap S, A Major J, Silverstein RLAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ATP Binding Cassette Transporter 1ATP-Binding Cassette Transporters
Adiponectin
Atherosclerosis
CD36 Antigens
Cells, Cultured
Diabetic Angiopathies
Foam Cells
Humans
Insulin
Lipoproteins, LDL
Macrophages
Scavenger Receptors, Class A
