Riemens S C, Van Tol A, Stulp B K, Dullaart R P
Department of Endocrinology, Cardiovascular Research Institute (COEUR), Erasmus University, Rotterdam, The Netherlands.
J Lipid Res. 1999 Aug;40(8):1467-74.
Lecithin:cholesteryl acyl transferase (LCAT), cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), and lipoprotein lipases are involved in high density lipoprotein (HDL) metabolism. We evaluated the influence of insulin sensitivity and of the TaqIB CETP gene polymorphism (B1B2) on plasma LCAT, CETP, and PLTP activities (measured with exogenous substrates) and their responses to hyperinsulinemia. Thirty-two non-diabetic men without hyperlipidemia were divided in quartiles of high (Q(1)) to low (Q(4)) insulin sensitivity. Plasma total cholesterol, very low + low density lipoprotein cholesterol, triglycerides, and apolipoprotein (apo) B were higher in Q(4) compared to Q(1) (P < 0.05 for all), whereas HDL cholesterol and apoA-I were lowest in Q(4) (P < 0.05 for both). Plasma LCAT activity was higher in Q(4) than in Q(1) (P < 0. 05) and PLTP activity was higher in Q(4) than in Q(2) (P < 0.05). Insulin sensitivity did not influence plasma CETP activity. Postheparin plasma lipoprotein lipase activity was highest and hepatic lipase activity was lowest in Q(1). Insulin infusion decreased PLTP activity (P < 0.05), irrespective of the degree of insulin sensitivity. The CETP genotype exerted no consistent effects on baseline plasma lipoproteins and LCAT, CETP, and PLTP activities. The decrease in plasma PLTP activity after insulin was larger in B1B1 than in B2B2 homozygotes (P < 0.05). These data suggest that insulin sensitivity influences plasma LCAT, PLTP, lipoprotein lipase, and hepatic lipase activities in men. As PLTP, LCAT, and hepatic lipase may enhance reverse cholesterol transport, it is tempting to speculate that high levels of these factors in association with insulin resistance could be involved in an antiatherogenic mechanism. A possible relationship between the CETP genotype and PLTP lowering by insulin warrants further study.
卵磷脂胆固醇酰基转移酶（LCAT）、胆固醇酯转运蛋白（CETP）、磷脂转运蛋白（PLTP）和脂蛋白脂肪酶参与高密度脂蛋白（HDL）代谢。我们评估了胰岛素敏感性以及TaqIB CETP基因多态性（B1B2）对血浆LCAT、CETP和PLTP活性（采用外源性底物测定）及其对高胰岛素血症反应的影响。32名无高脂血症的非糖尿病男性按胰岛素敏感性从高（Q(1)）到低（Q(4)）分为四分位数。与Q(1)相比，Q(4)中的血浆总胆固醇、极低密度脂蛋白+低密度脂蛋白胆固醇、甘油三酯和载脂蛋白（apo）B更高（所有P均<0.05），而HDL胆固醇和apoA-I在Q(4)中最低（两者P均<0.05）。血浆LCAT活性在Q(4)中高于Q(1)（P<0.05），PLTP活性在Q(4)中高于Q(2)（P<0.05）。胰岛素敏感性不影响血浆CETP活性。肝素后血浆脂蛋白脂肪酶活性在Q(1)中最高，肝脂肪酶活性在Q(1)中最低。胰岛素输注降低了PLTP活性（P<0.05），与胰岛素敏感性程度无关。CETP基因型对基线血浆脂蛋白以及LCAT、CETP和PLTP活性没有一致的影响。胰岛素后血浆PLTP活性的降低在B1B1纯合子中比在B2B2纯合子中更大（P<0.05）。这些数据表明胰岛素敏感性影响男性的血浆LCAT、PLTP、脂蛋白脂肪酶和肝脂肪酶活性。由于PLTP、LCAT和肝脂肪酶可能增强胆固醇逆向转运，因此很容易推测这些因子与胰岛素抵抗相关的高水平可能参与抗动脉粥样硬化机制。CETP基因型与胰岛素降低PLTP之间的可能关系值得进一步研究。
