Glycadia, Inc, Philadelphia, PA 19103, USA.
Metabolism. 2010 May;59(5):658-63. doi: 10.1016/j.metabol.2009.09.010. Epub 2009 Nov 18.
Increased nonenzymatic glycation of apolipoprotein (apo) B-containing lipoproteins impairs uptake and metabolism by the high-affinity low-density lipoprotein receptor and is one of the postsecretory modifications contributory to accelerated atherosclerosis in diabetes. The present study evaluated in vitro and in vivo effects of 2,2-chlorophenylaminophenylacetate to probe the influence of glycated lipoprotein on cholesterol homeostasis. This compound prevented the increased formation of glycated products in low-density lipoprotein incubated with 200 mmol/L glucose and the increased cholesteryl ester synthesis in THP-1 macrophages induced by apo B-containing lipoproteins preincubated with high glucose concentration. The elevated circulating concentrations of glycated lipoprotein and cholesterol and higher vascular levels of lipid peroxidation products observed in streptozotocin diabetic rats compared with nondiabetic controls were significantly reduced in diabetic animals treated for 6 months with test compound. These results are the first to demonstrate that inhibiting nonenzymatic glycation of apo B-containing lipoproteins ameliorates abnormalities contributory to hypercholesterolemia and atherogenic risk in diabetes.
载脂蛋白（apo）B 脂蛋白的非酶糖基化增加会损害高亲和力低密度脂蛋白受体的摄取和代谢，是糖尿病加速动脉粥样硬化的后天修饰之一。本研究通过体外和体内实验评估了 2,2-氯苯氨基苯乙酸对糖基化脂蛋白影响胆固醇稳态的作用。该化合物可预防在 200mmol/L 葡萄糖孵育的低密度脂蛋白中形成更多的糖基化产物，也可预防在高糖浓度预孵育载 apoB 脂蛋白诱导的 THP-1 巨噬细胞中胆固醇酯合成增加。与非糖尿病对照组相比，链脲佐菌素糖尿病大鼠的循环糖基化脂蛋白和胆固醇浓度升高，血管内脂质过氧化产物水平升高，用该试验化合物治疗 6 个月的糖尿病动物明显降低。这些结果首次证明，抑制 apoB 脂蛋白的非酶糖基化可改善高胆固醇血症和糖尿病致动脉粥样硬化风险的异常。
