Hamada Y, Araki N, Horiuchi S, Hotta N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Nephrol Dial Transplant. 1996;11 Suppl 5:95-8. doi: 10.1093/ndt/11.supp5.95.
In order to confirm the link between nonenzymatic glycation and the polyol pathway, we observed the effect of treatment with epalrestat (Ep), an aldose reductase inhibitor, on the concentration of advanced glycation end-products (AGEs) in erythrocytes from diabetic patients. We also examined the effect of the drug on erythrocyte fructose 3-phosphate (F3P), a novel metabolite that has been reported to relate to the polyol pathway, and ascertained the glycation capability of F3P and its possible breakdown product, 3-deoxyglucosone (3DG), by incubating the metabolites with bovine serum albumin (BSA). Incubation of BSA with F3P or 3DG resulted in a greater production of AGEs in comparison with the incubation with glucose or fructose. F3P was significantly increased in erythrocytes from diabetic patients compared with those from nondiabetic individuals and was lower in patients who had been treated with Ep than in those who were free from the compound. A treatment of patients with Ep for 1 month resulted in a significant decrease in F3P. Erythrocyte AGEs were significantly elevated in diabetic patients compared with nondiabetic individuals and tended to be lower in patients taking Ep than in those without Ep. Administration of Ep for 2 months decreased AGEs. These results show that the polyol pathway is likely to play a substantial role in the nonenzymatic glycation of proteins and the suppression of E3P as well as AGEs by an aldose reductase inhibitor may explain in part the preventive effect of the drug on diabetic complications.
为了证实非酶糖基化与多元醇途径之间的联系，我们观察了醛糖还原酶抑制剂依帕司他（Ep）对糖尿病患者红细胞中晚期糖基化终产物（AGEs）浓度的影响。我们还研究了该药物对红细胞果糖-3-磷酸（F3P）的影响，F3P是一种据报道与多元醇途径相关的新型代谢产物，并通过将这些代谢产物与牛血清白蛋白（BSA）孵育来确定F3P及其可能的分解产物3-脱氧葡萄糖酮（3DG）的糖基化能力。与用葡萄糖或果糖孵育相比，BSA与F3P或3DG孵育会产生更多的AGEs。与非糖尿病个体的红细胞相比，糖尿病患者红细胞中的F3P显著增加，并且接受Ep治疗的患者的F3P低于未使用该化合物的患者。对患者使用Ep治疗1个月导致F3P显著降低。与非糖尿病个体相比，糖尿病患者的红细胞AGEs显著升高，服用Ep的患者的AGEs往往低于未服用Ep的患者。使用Ep治疗2个月可降低AGEs。这些结果表明，多元醇途径可能在蛋白质的非酶糖基化中起重要作用，醛糖还原酶抑制剂对E3P和AGEs的抑制作用可能部分解释了该药物对糖尿病并发症的预防作用。
