CRUCIAL ROLE OF ALDOSE REDUCTASE-ACTIVITY AND PLASMA-GLUCOSE LEVEL IN SORBITOL ACCUMULATION IN ERYTHROCYTES FROM DIABETIC-PATIENTS
CRUCIAL ROLE OF ALDOSE REDUCTASE-ACTIVITY AND PLASMA-GLUCOSE LEVEL IN SORBITOL ACCUMULATION IN ERYTHROCYTES FROM DIABETIC-PATIENTS
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DOI：
10.2337/diabetes.40.10.1233
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发表时间：
1991-10-01
期刊：
影响因子：
7.7
通讯作者：
RASKIN, P
中科院分区：
文献类型：
--
作者：
HAMADA, Y;KITOH, R;RASKIN, P
糖尿病患者的组织中山梨醇水平升高。 尽管组织山梨醇水平与血浆葡萄糖水平相关，但在具有相似血浆葡萄糖水平的糖尿病患者中观察到山梨醇水平存在很大差异。 组织山梨醇水平的这种变化可能是由于醛糖还原酶（将葡萄糖转化为山梨醇的酶）活性的差异所致。 在这项研究中，我们从 31 名糖尿病患者和 6 名非糖尿病对照受试者的红细胞中分离出醛糖还原酶，测量其活性，并将其与同时测量的红细胞山梨醇水平进行比较。 与对照组相比，糖尿病患者的红细胞醛糖还原酶活性增加（28.1 +/- 1.4 vs. 22.4 +/- 1.7 nmol.min-1.g-1 Hb，P < 0.05），但糖尿病患者的醛糖还原酶活性大约有三倍的差异。 所有个体的红细胞醛糖还原酶活性和空腹血糖水平与红细胞山梨醇水平显着相关（分别为r = 0.48，P < 0.005 和r = 0.63，P < 0.005）。 对于任何给定的血糖水平，醛糖还原酶活性高的患者的山梨醇水平高于酶活性低的患者。 由K(m)和V(max)值计算的山梨醇生成率与红细胞山梨醇水平有较好的相关性(r = 0.80，P < 0.005)，红细胞山梨醇水平与醛糖还原酶活性与血浆葡萄糖水平的乘积也有良好的相关性(r = 0.70，P < 0.005)。 我们得出的结论是，醛糖还原酶活性和环境血浆葡萄糖浓度都是糖尿病患者组织中积累的山梨醇水平的重要决定因素。
Increased sorbitol levels have been demonstrated in tissues of diabetic patients. Although tissue sorbitol levels correlate with plasma glucose levels, a large variability in sorbitol levels has been observed among diabetic patients with similar plasma glucose levels. This variability in tissue sorbitol levels may be due to differences in the activity of aldose reductase, the enzyme that converts glucose to sorbitol. In this study, we isolated aldose reductase from erythrocytes of 31 diabetic patients and 6 nondiabetic control subjects, measured its activity, and compared it to simultaneously measured erythrocyte sorbitol levels. The activity of erythrocyte aldose reductase was increased in diabetic patients compared with control subjects (28.1 +/- 1.4 vs. 22.4 +/- 1.7 nmol . min-1 . g-1 Hb, P < 0.05), but there was an approximately threefold variation in aldose reductase activity among diabetic patients. Erythrocyte aldose reductase activity and fasting plasma glucose levels significantly correlated with the erythrocyte sorbitol level in all individuals (r = 0.48, P < 0.005 and r = 0.63, P < 0.005, respectively). The sorbitol level was higher in patients with high aldose reductase activity than in those who had low enzyme activity for any given level of glycemia. The sorbitol production rate calculated from K(m) and V(max) values showed a better correlation with the erythrocyte sorbitol level (r = 0.80, P < 0.005), and there was also a good correlation between the erythrocyte sorbitol level and the product of aldose reductase activity by plasma glucose level (r = 0.70, P < 0.005). We conclude that both aldose reductase activity and the ambient plasma glucose concentration are important determinants of the level of sorbitol that accumulates in tissues of diabetic patients.