Insulin suppresses HDL-mediated cholesterol efflux from macrophages through inhibition of neutral cholesteryl ester hydrolase and ATP-binding cassette transporter G1 expressions.

Maki Yamashita, Naoki Tamasawa, Kota Matsuki, Jutaro Tanabe, Hiroshi Murakami, Jun Matsui, Toshihiro Suda

Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori, Japan.

Journal of atherosclerosis and thrombosis 2010 Nov 27

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We studied the effect of insulin on HDL-mediated cholesterol efflux from macrophages. The potential involvement of cholesteryl ester hydrolysis and membrane cholesterol transport was also addressed. Human monocyte-derived THP-1 cells were developed into macrophages. Cholesterol efflux was measured by incubating macrophages, labeled with [³H]-cholesterol, with HDL for 24 h. The cells were treated with insulin (0-500 nM) for 30 min prior to the addition of HDL. To investigate the molecular mechanisms of the effect of insulin, the expressions of neutral cholesteryl ester hydrolase (nCEH) and ATP-binding cassette transporter (ABC) G1 were analyzed. Insulin inhibited, in a concentration-dependent manner, HDL-mediated cholesterol efflux from macrophages. Insulin also inhibited the enzyme activity of nCEH and its mRNA and protein expression in cells. Insulin also suppressed the expressions of mRNA and protein for ABCG1. Insulin inhibits HDL-mediated cholesterol efflux from macrophages, which may result from the suppression of nCEH and ABCG1 expressions. Our findings show part of the potential molecular mechanism of atherogenesis in type 2 diabetes with hyperinsulinemia.

Citation

Maki Yamashita, Naoki Tamasawa, Kota Matsuki, Jutaro Tanabe, Hiroshi Murakami, Jun Matsui, Toshihiro Suda. Insulin suppresses HDL-mediated cholesterol efflux from macrophages through inhibition of neutral cholesteryl ester hydrolase and ATP-binding cassette transporter G1 expressions. Journal of atherosclerosis and thrombosis. 2010 Nov 27;17(11):1183-9