STUDIES OF HEPATIC RECEPTORS FOR GLYCOPROTEINS

一个人的细胞定位和碳水化合物特异性 大鼠肝窦细胞糖蛋白识别系统 已经确定。 内皮细胞的纯化制剂， 枯否细胞和实质细胞已通过原位 胶原酶肝脏灌注，Percoll梯度离心 和离心淘析。 125 I标记半乳糖类粘蛋白 （AGOR），一种N-乙酰葡糖胺封端的糖蛋白， 选择性和特异性地被内皮细胞在体外摄取 细胞 葡萄糖和葡萄糖-白蛋白结合物竞争性地 在很宽的浓度范围内抑制了这一吸收过程。 禁食大鼠的细胞摄取增强，但细胞摄取 从禁食或喂养的糖尿病大鼠是正常的。 体内肝脏 糖尿病患者对125 I-AGOR的摄取和释放均比正常人慢， 正常老鼠 推测：1）肝受体， 识别N-乙酰葡糖胺/甘露糖终止的糖蛋白是 主要位于内皮细胞上，2）这些受体是 葡萄糖敏感，3）禁食增加这些数量 受体和4）糖尿病废除这种影响的禁食 并损害该受体在体内的功能。 这些发现 提示了糖蛋白代谢异常机制， 糖尿病的 这种碳水化合物识别系统可能起着 在去除潜在的自我毁灭性的 糖蛋白溶酶体水解酶和其它糖蛋白酶 从正常生理条件下的循环和 疾病状态。

The cellular location and carbohydrate specificities of a glycoprotein recognition system on rat hepatic sinusoidal cells have been determined. Purified preparations of endothelial, Kupffer and parenchymal cells have been prepared by in situ collagenase liver perfusion, centrifugation on Percoll gradients and centrifugal elutriation. 125I-labeled agalactoorosomucoid (AGOR), an N-acetylglucosamine-terminated glycoprotein, was selectively and specifically taken up in vitro by endothelial cells. Glucose and a glucose-albumin conjugate competitively inhibited this uptake process over a wide range of concentrations. Uptake by cells from fasted rats was enhanced, but uptake by cells from fasted or fed diabetic rats was normal. The in vivo hepatic uptake and catabolism of 125I-AGOR were slower in diabetic than normal rats. It is inferred that 1) the hepatic receptors which recognize N-acetylglucosamine/mannose terminated glycoproteins are located predominantly on endothelial cells, 2) these receptors are glucose sensitive, 3) fasting increases the number of these receptors and 4) diabetes mellitus abolishes this effect of fasting and impairs the function of this receptor in vivo. These findings suggest a mechanism for abnormal glycoprotein metabolism in diabetes mellitus. This carbohydrate recognition system may play an important role in the removal of potentially autodestructive glycoprotein lysosomal hydrolases and other glycoprotein enzymes from the circulation under normal physiological conditions and in disease states.