Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Aomori, Japan.
J Atheroscler Thromb. 2010 Nov 27;17(11):1183-9. doi: 10.5551/jat.4721. Epub 2010 Aug 20.
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.
本研究旨在探讨胰岛素对巨噬细胞源性高密度脂蛋白（HDL）介导的胆固醇外流的影响，并探讨胆固醇酯水解和膜胆固醇转运的潜在作用。
将人单核细胞来源的 THP-1 细胞诱导分化为巨噬细胞。孵育标记有[³H]-胆固醇的巨噬细胞 24 小时后，测量胆固醇外流。在加入 HDL 之前，用胰岛素（0-500 nM）处理细胞 30 分钟。为了研究胰岛素作用的分子机制，分析了中性胆固醇酯水解酶（nCEH）和 ATP 结合盒转运体（ABC）G1 的表达。
胰岛素呈浓度依赖性抑制 HDL 介导的巨噬细胞源性胆固醇外流。胰岛素还抑制了细胞内 nCEH 的酶活性及其 mRNA 和蛋白表达。胰岛素还抑制了 ABCG1 的 mRNA 和蛋白表达。
胰岛素抑制 HDL 介导的巨噬细胞源性胆固醇外流，这可能是由于抑制了 nCEH 和 ABCG1 的表达。我们的研究结果显示了伴有高胰岛素血症的 2 型糖尿病发生动脉粥样硬化的部分潜在分子机制。
