De Mattia G, Laurenti O, Bravi C, Ghiselli A, Iuliano L, Balsano F
Institute of First Clinical Medicine, University La Sapienza, Rome, Italy.
Metabolism. 1994 Aug;43(8):965-8. doi: 10.1016/0026-0495(94)90175-9.
Diabetic patients undergo a chronic oxidative stress. This phenomenon is demonstrated by low levels of reduced glutathione (GSH) levels. The NADPH used by glutathione reductase for the reduction of oxidized glutathione (GSSG) to GSH is also used by aldose reductase for the reduction of glucose to sorbitol through the polyol pathway. The competition for NADPH could be responsible for the decreased glutathione levels found in non-insulin-dependent diabetic patients. For this purpose, we investigated the effect of polyol pathway inhibition on the glutathione redox status in these patients. We measured GSH and GSSG levels in erythrocytes of non-insulin-dependent diabetic patients (n = 15) before and after 1 week of treatment with placebo, followed by 1 week of treatment with an aldose reductase inhibitor (tolrestat 200 mg/dl). We found lower GSH levels (7.7 +/- 1.4 mumol/g hemoglobin [Hb]), higher GSSG levels (0.35 +/- 0.09 mumol/g Hb), and lower GSH/GSSG ratios (23.9 +/- 7.7) in diabetics compared with controls (n = 15; 9.8 +/- 0.8 mumol/g Hb, P < .001; 0.17 +/- 0.02, P < .001; and 58.3 +/- 9.1, P < .001, respectively). We did not demonstrate any statistical difference after 1 week of treatment with placebo. In contrast, the treatment with tolrestat induced a significant increase in GSH (8.9 +/- 0.7 mumol/g Hb, P < .01), a decrease in GSSG (0.25 +/- 0.06 mumol/g Hb, P < .02), and an increase in the GSH/GSSG ratio (37.3 +/- 8.4, P < .01). These data strongly support the hypothesis that the polyol pathway plays an important role in the impairment of the glutathione redox status in diabetic patients.
糖尿病患者会经历慢性氧化应激。这种现象表现为还原型谷胱甘肽（GSH）水平较低。谷胱甘肽还原酶用于将氧化型谷胱甘肽（GSSG）还原为GSH所使用的烟酰胺腺嘌呤二核苷酸磷酸（NADPH），也被醛糖还原酶用于通过多元醇途径将葡萄糖还原为山梨醇。对NADPH的竞争可能是导致非胰岛素依赖型糖尿病患者谷胱甘肽水平降低的原因。为此，我们研究了多元醇途径抑制对这些患者谷胱甘肽氧化还原状态的影响。我们测量了15名非胰岛素依赖型糖尿病患者在接受1周安慰剂治疗前后以及随后接受1周醛糖还原酶抑制剂（托瑞司他200mg/dl）治疗前后红细胞中的GSH和GSSG水平。我们发现，与15名对照组患者相比（分别为9.8±0.8μmol/g血红蛋白[Hb]，P<.001；0.17±0.02，P<.001；以及58.3±9.1，P<.001），糖尿病患者的GSH水平较低（7.7±1.4μmol/g Hb），GSSG水平较高（0.35±0.09μmol/g Hb），GSH/GSSG比值较低（23.9±7.7）。在接受1周安慰剂治疗后，我们未发现任何统计学差异。相比之下，托瑞司他治疗导致GSH显著增加（8.9±0.7μmol/g Hb，P<.01），GSSG降低（0.25±0.06μmol/g Hb，P<.02），以及GSH/GSSG比值增加（37.3±8.4，P<.01）。这些数据有力地支持了以下假设：多元醇途径在糖尿病患者谷胱甘肽氧化还原状态受损中起重要作用。
