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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Yamashita
Maki
M
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori, Japan.
Tamasawa
Naoki
N
Matsuki
Kota
K
Tanabe
Jutaro
J
Murakami
Hiroshi
H
Matsui
Jun
J
Suda
Toshihiro
T
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D057057:Serine Proteases; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism*
C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D007328:Insulin; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D002784:Cholesterol; C514712:Nceh1 protein, mouse; D002787:Sterol Esterase; D057057:Serine Proteases