Hatton M W, Southward S, Ross-Ouellet B, Richardson M, Winocour P D
Department of Pathology, McMaster University.
J Lab Clin Med. 1993 Apr;121(4):588-97.
The incidence of nonenzymatic glycation of proteins within the hyperglycemic environment of diabetic plasma is increased compared with that in normal (i.e., nondiabetic) plasma. Whether glycation in vivo alters the behavior of proteins within the circulation is not well understood. Glycated fibrinogen, although not detected in normal rabbit plasma, was isolated from diabetic rabbit plasmas (glucose concentration 12 to 39 mmol/L) and separated from unglycated fibrinogen by boronate chromatography. The yield of glycated fibrinogen, which amounted to 3% to 6% of total fibrinogen, correlated with the content of plasma glucose. Glycated and unglycated fibrinogens facilitated aggregation of normal or diabetic platelets to a similar extent after adding adenosine-5'-diphosphate. Normal platelets stimulated by adenosine-5'-diphosphate bound more iodine 131-glycated fibrinogen than iodine 125-unglycated fibrinogen (p < 0.05), whereas the quantities of glycated and unglycated fibrinogens bound by diabetic platelets were not significantly different. When coinjected intravenously into normal or diabetic rabbits, 131I-glycated fibrinogen was cleared from the circulation faster than 125I-unglycated fibrinogen although the catabolic rates, measured as half-life, were not significantly different. At equilibrium, glycated fibrinogen was distributed significantly more in the extravascular and less in the vascular compartments of the normal and diabetic rabbit compared with the unglycated type. After balloon injury to the aorta in vivo, the unglycated/glycated ratio of radiolabeled fibrinogens associated with the platelet monolayer was 0.94, whereas for the damaged subendothelium the ratio was 1.20 (p < 0.005). We conclude that glycation in vivo changes several metabolic characteristics of fibrinogen in the normal and diabetic rabbit.
与正常（即非糖尿病）血浆相比，糖尿病血浆高血糖环境中蛋白质的非酶糖基化发生率增加。体内糖基化是否会改变循环中蛋白质的行为尚不清楚。糖化纤维蛋白原虽在正常兔血浆中未检测到，但可从糖尿病兔血浆（葡萄糖浓度为12至39 mmol/L）中分离出来，并通过硼酸酯色谱法与未糖化的纤维蛋白原分离。糖化纤维蛋白原的产量占总纤维蛋白原的3%至6%，与血浆葡萄糖含量相关。添加5'-二磷酸腺苷后，糖化和未糖化的纤维蛋白原促进正常或糖尿病血小板聚集的程度相似。5'-二磷酸腺苷刺激的正常血小板结合131I-糖化纤维蛋白原比125I-未糖化纤维蛋白原更多（p<0.05），而糖尿病血小板结合的糖化和未糖化纤维蛋白原数量无显著差异。当静脉内共同注射到正常或糖尿病兔体内时，131I-糖化纤维蛋白原从循环中清除的速度比125I-未糖化纤维蛋白原快，尽管以半衰期衡量的分解代谢率无显著差异。在平衡状态下，与未糖化类型相比，糖化纤维蛋白原在正常和糖尿病兔的血管外分布明显更多，而在血管内分布更少。体内主动脉球囊损伤后，与血小板单层相关的放射性标记纤维蛋白原的未糖化/糖化比率为0.94，而受损内皮下的比率为1.20（p<0.005）。我们得出结论，体内糖基化改变了正常和糖尿病兔体内纤维蛋白原的几种代谢特征。
