Handberg Aase, Levin Klaus, Højlund Kurt, Beck-Nielsen Henning
Department of Clinical Biochemistry, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark.
Circulation. 2006 Sep 12;114(11):1169-76. doi: 10.1161/CIRCULATIONAHA.106.626135. Epub 2006 Sep 4.
Macrophage CD36 scavenges oxidized low-density lipoprotein, leading to foam cell formation, and appears to be a key proatherogenic molecule. Increased expression of CD36 has been attributed to hyperglycemia and to defective macrophage insulin signaling in insulin resistance. Premature atherosclerosis is the major cause of morbidity and mortality in type 2 diabetes. Here, we report the identification of a soluble form of CD36 (sCD36) in plasma and hypothesize that sCD36 would be elevated in patients with type 2 diabetes and insulin resistance.
sCD36 in plasma was demonstrated by immunopurification and Western blotting. We established ELISA assays to determine sCD36 in plasma and measured sCD36 in obese type 2 diabetic patients, obese nondiabetic relatives, and obese and lean control subjects. sCD36 was markedly elevated in type 2 diabetic patients compared with both lean (5-fold) and obese (2- to 3-fold) control subjects. There was a strong, inverse correlation between sCD36 and insulin-stimulated glucose disposal and a direct correlation with fasting plasma glucose, fasting insulin, and body mass index.
Our study demonstrates sCD36 in plasma for the first time. sCD36 is highly related to risk factors of accelerated atherosclerosis in type 2 diabetes such as insulin resistance and glycemic control, and we propose that sCD36 might represent a marker of the metabolic syndrome and a potential surrogate marker of atherosclerosis.
巨噬细胞CD36可清除氧化型低密度脂蛋白,导致泡沫细胞形成,似乎是一种关键的促动脉粥样硬化分子。CD36表达增加归因于高血糖以及胰岛素抵抗中巨噬细胞胰岛素信号传导缺陷。动脉粥样硬化过早发生是2型糖尿病发病和死亡的主要原因。在此,我们报告在血浆中鉴定出可溶性CD36(sCD36),并推测2型糖尿病和胰岛素抵抗患者的sCD36会升高。
通过免疫纯化和蛋白质印迹法证实血浆中存在sCD36。我们建立了酶联免疫吸附测定法来测定血浆中的sCD36,并测量了肥胖2型糖尿病患者、肥胖非糖尿病亲属以及肥胖和瘦对照受试者的sCD36。与瘦对照受试者(5倍)和肥胖对照受试者(2至3倍)相比,2型糖尿病患者的sCD36显著升高。sCD36与胰岛素刺激的葡萄糖处置之间存在强烈的负相关,与空腹血糖、空腹胰岛素和体重指数呈正相关。
我们的研究首次证实血浆中存在sCD36。sCD36与2型糖尿病中加速动脉粥样硬化的危险因素如胰岛素抵抗和血糖控制高度相关,我们提出sCD36可能代表代谢综合征的一个标志物以及动脉粥样硬化的一个潜在替代标志物。