Evidence for accelerated rates of glutathione utilization and glutathione depletion in adolescents with poorly controlled type 1 diabetes
Evidence for accelerated rates of glutathione utilization and glutathione depletion in adolescents with poorly controlled type 1 diabetes
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DOI：
10.2337/diabetes.54.1.190
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发表时间：
2005-01-01
期刊：
影响因子：
7.7
通讯作者：
Mauras, N
中科院分区：
文献类型：
--
作者：
Darmaun, D;Smith, SD;Mauras, N
谷胱甘肽是存在于红细胞中的一种重要的抗氧化剂，在1型糖尿病中有报道，但这种消耗的机制尚未完全确定。谷氨酰胺耗竭可通过合成减少、利用增加或两者的组合而发生。为了解决这一问题，对16名糖尿病青少年进行了5小时L-[3，3-H-2（2）]半胱氨酸输注，分为控制良好组和控制不良组，并对8名健康的非糖尿病青少年进行了5小时L-[3，3-H-2（2）]半胱氨酸输注，作为对照组（HbA（1c）分别为6.3 +/- 0.2、10.5 +/- 0.6和4.8 +/- 0.1%）。从H-2（2）-半胱氨酸掺入到血液谷胱甘肽中测定谷胱甘肽的合成率。我们观察到：1）与控制良好的患者相比，控制不良的患者红细胞半胱氨酸浓度低41（2）血糖控制良好和血糖控制不佳患者的红细胞谷胱甘肽浓度分别比健康志愿者低29%和36%;和3）谷胱甘肽的分数合成率，尽管在良好控制的和健康的受试者中相似（每天83 +/- 14 vs. 82 +/- 11%），控制不良组显著更高（每天141 +/- 23%，P = 0.038）。这些研究结果表明，在糖尿病青少年中，控制不良与血液谷胱甘肽和半胱氨酸的显著消耗有关，这是由于谷胱甘肽利用率增加。这种减弱的抗氧化防御可能在糖尿病并发症的发病机制中发挥作用。
Depletion of glutathione, an important antioxidant present in red cells, has been reported in type 1 diabetes, but the mechanism of this depletion has not been fully characterized. Glutathione depletion can occur through decreased synthesis, increased utilization, or a combination of both. To address this issue, 5-h infusions of L-[3,3-H-2(2)]cysteine were performed in 16 diabetic adolescents divided into a well-controlled and a poorly controlled group and in eight healthy nondiabetic teenagers as control subjects (HbA(1c) 6.3 +/- 0.2, 10.5 +/- 0.6, and 4.8 +/- 0.1% respectively). Glutathione fractional synthesis rate was determined from H-2(2)-cysteine incorporation into blood glutathione. We observed that 1) erythrocyte cysteine concentration was 41% lower in poorly controlled patients compared with well-controlled patients (P = 0.009); 2) erythrocyte glutathione concentration was similar to29% and similar to36% lower in well-controlled and poorly controlled patients compared with healthy volunteers; and 3) the fractional synthesis rate of glutathione, although similar in well-controlled and healthy subjects (83 +/- 14 vs. 82 +/- 11% per day), was substantially higher in the poorly controlled group (141 +/- 23% per day, P = 0.038). These findings suggest that in diabetic adolescents, poor control is associated with a significant depletion of blood glutathione and cysteine, due to increased rates of glutathione utilization. This weakened antioxidant defense may play a role in the pathogenesis of diabetes complications.