Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24 h insulin infusion in healthy subjects and type 2 diabetic patients
Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24 h insulin infusion in healthy subjects and type 2 diabetic patients
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DOI：
10.1016/j.atherosclerosis.2010.10.028
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发表时间：
2011-02-01
期刊：
影响因子：
5.3
通讯作者：
Dullaart, Robin P. F.
中科院分区：
文献类型：
--
作者：
Kappelle, Paul J. W. H.;Lambert, Gilles;Dullaart, Robin P. F.
目的：枯草杆菌前蛋白转换酶9(PCSK9)可促进低密度脂蛋白(LDL)受体降解，从而为低密度脂蛋白(LDL)代谢提供关键途径。在小鼠模型中，胰岛素可上调PCSK9的表达。我们研究了外源性高胰岛素血症对2型糖尿病患者血浆PCSK9水平的影响。方法：对8例健康男性和8例男性2型糖尿病患者进行24 h中度高胰岛素葡萄糖钳夹试验(30mU/kg/h)。结果：胰岛素可降低健康人和糖尿病患者血浆低密度脂蛋白胆固醇和载脂蛋白B水平(P均<0.01)，降低甘油三酯水平(P<0.01)。正常人和糖尿病患者血浆PCSK9水平无明显变化(中位数(四分位数变化)-23(-63~25)%，P=0.50)，糖尿病患者(变化4(-17~44)%，P=0.20)。胰岛素作用24 h后，个体低密度脂蛋白胆固醇、载脂蛋白B和甘油三酯的绝对和相对变化与PCSK9的变化无关(P>；均为0.15)。结论：健康人和2型糖尿病患者暴露于中等程度的高胰岛素血症后，血浆PCSK9水平不会升高。(C)2010爱思唯尔爱尔兰有限公司。保留所有权利。
Purpose: Proprotein convertase subtilisin-kexin type 9 (PCSK9) promotes low density lipoprotein (LDL) receptor degradation, thereby providing a key pathway for LDL metabolism. PCSK9 mRNA expression may be upregulated by insulin in murine models. Here we examined effects of exogenous hyperinsulinemia on plasma PCSK9 levels in humans without and with type 2 diabetes mellitus.Methods: A 24 h moderately hyperinsulinemic glucose clamp (30 mU/kg/h) was performed in 8 healthy men and 8 male type 2 diabetic patients. Plasma PCSK9 was measured using a sandwich enzyme-linked immunosorbent assay.Results: Plasma LDL cholesterol and apolipoprotein B were lowered by insulin in healthy subjects and diabetic patients (P < 0.01 for all), whereas triglycerides were also decreased in healthy subjects (P < 0.01). Plasma PCSK9 levels remained unchanged in healthy subjects (median (interquartile range) change, -23 (-63 to 25) %, P = 0.50) and in diabetic patients (change, 4 (-17 to 44) %, P = 0.20). Individual absolute and relative changes in LDL cholesterol, apolipoprotein B and triglycerides after 24 h of insulin were unrelated to changes in PCSK9 (P > 0.15 for all).Conclusion: Plasma PCSK9 levels are not increased by exposure to moderate 24 h hyperinsulinemia in healthy and type 2 diabetic individuals. (C) 2010 Elsevier Ireland Ltd. All rights reserved.