Relationship between glutathione synthesis and cystine+glycine in diabetes

有证据表明，糖尿病患者的还原型谷胱甘肽(GSH)浓度较低，表明抗氧化防御能力受损。白内障和视网膜病变被认为与谷胱甘肽状态受损有关。糖尿病状态下谷胱甘肽耗竭的机制尚未建立。可以合理地提出一种双重机制，在这种机制中，与疾病相关的过氧化应激导致GSH的加速丧失，而由于前体氨基酸半胱氨酸和甘氨酸的可获得性降低，合成足够量的GSH以满足需求的能力受到损害。利用稳定同位素技术，我们将测量谷胱甘肽的合成速度，并将这一测量与成年糖尿病患者和健康成年人的半胱氨酸和甘氨酸的合成联系起来。与NIDDM和IDDM年龄相匹配的8名NIDDM、8名IDDM和16名健康对照组将分4种情况入院：常规饮食(不补充)、补充半胱氨酸、补充甘氨酸和同时补充甘氨酸和半胱氨酸。在每种情况下，将使用稳定同位素和质谱仪技术来确定半胱氨酸、甘氨酸和亮氨酸的动力学以及红细胞和白细胞谷胱甘肽的合成速度。在饮食中补充甘氨酸、半胱氨酸和甘氨酸加半胱氨酸后，这些测量将重复进行。到目前为止，我们已经招募了5名糖尿病患者和2名对照。初步数据显示，与对照组相比，糖尿病患者体内的过氧化氢浓度较高，淋巴细胞GSH浓度和合成速率较低。添加半胱氨酸后，GSH含量和绝对合成速率提高了12倍。提示补充半胱氨酸可改善GSH动态平衡。

Evidence suggests that patients with diabetes have lower concentrations of reduced glutathione (GSH) indicative of impaired antioxidant defenses. Cataracts and retinopathy have been linked to impaired glutathione status. The mechanisms responsible for glutathione depletion in the diabetic state have not been established. It is reasonable to propose that a dual mechanism is operative in which the peroxidative stress associated with the disease leads to accelerated loss of GSH while the ability to synthesize GSH in sufficient quantities to meet the increased need is compromised because of decreased availability of the precursor amino acids cysteine and glycine. Using stable isotope techniques, we will measure the rate of synthesis of glutathione and relate this measurement to the syntheses of cysteine and glycine in adult patients with diabetes and in healthy adults. Eight NIDDM, 8 IDDM, and 16 healthy controls matched for age with the NIDDM and IDDM will be admitted on 4 occasions: after usual diet (no supplementation), after supplementation with cysteine, after supplementation with glycine, and after supplementation with both glycine and cysteine. During each occasion stable isotope and mass spectometry techniques will be used to determine cysteine, glycine and leucine kinetics as well as the rate of synthesis of erythrocyte and leukocyte glutathione. These measurements will be repeated after dietary supplementation with glycine, cysteine, and glycine plus cysteine. Thus far, we have enrolled 5 diabetic patients and 2 controls. Preliminary data shows that compared to controls, diabetics have a higher concentration of hydroperoxides, and lower lymphocyte GSH concentration as well as synthesis rate. With cysteine supplementaion GSH concentration and absolute synthesis rate increased twelve fold. This suggests that cysteine supplementaion can improve GSH homeostasis.