De Mattia G, Bravi M C, Laurenti O, Cassone-Faldetta M, Armiento A, Ferri C, Balsano F
Andrea Cesalpino Foundation, Chair of I Clinica Medica, University of Rome La Sapienza, Italy.
Metabolism. 1998 Aug;47(8):993-7. doi: 10.1016/s0026-0495(98)90357-2.
To evaluate the relationship between oxidative stress and glucose metabolism, insulin sensitivity and intraerythrocytic reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio were measured in 10 non-insulin-dependent diabetes mellitus (NIDDM) patients and 10 healthy subjects before and after the intravenous administration of GSH. In particular, after baseline insulin sensitivity was assessed by a 2-hour euglycemic hyperinsulinemic clamp, either glutathione (1.35 g x m2 x min(-1)) or placebo (saline) were infused over a period of 1 hour. The same protocol was repeated at a 1-week interval, in cross-over, according to a randomized, single-blind design. In healthy subjects, baseline intraerythrocytic GSH/GSSG ratio (P < .0005) and total glucose uptake (P < .005) were significantly higher than in NIDDM patients. In the same subjects, GSH infusion significantly increased total glucose uptake (from 37.1 +/- 6.7 micromol kg(-1) x min(-1) to 39.5 +/- 7.7 micromol x kg(-1) x min(-1), P < .05), whereas saline infusion was completely ineffective. In addition, the mean intraerythrocytic GSH/GSSG ratio significantly increased after GSH infusion (from 21.0 +/- 0.9 to 24.7 +/- 1.3, P < .05). Similar findings were found in diabetic patients, in whom GSH infusion significantly increased both total glucose uptake (from 25.3 +/- 9.0 micromol x kg(-1) x min(-1) to 31.4 +/- 10.0 micromol x kg(-1) x min(-1), P < .001) and intraerythrocytic GSH/GSSG ratio (from 14.8 +/- 4.1 to 21.7 +/- 6.7, P < .01). Pooling diabetic patients and controls, significant correlations were found between intraerythrocytic GSH/GSSG ratio and total glucose uptake (r = .425, P < .05), as well as between increments of the same variables after GSH infusion (r = .518, P < .05). In conclusion, our data support the hypothesis that abnormal intracellular GSH redox status plays an important role in reducing insulin sensitivity in NIDDM patients. Accordingly, intravenous GSH infusion significantly increased both intraerythrocytic GSH/GSSG ratio and total glucose uptake in the same patients.
为评估氧化应激与葡萄糖代谢之间的关系，在10例非胰岛素依赖型糖尿病（NIDDM）患者和10名健康受试者静脉注射谷胱甘肽（GSH）前后，测量了胰岛素敏感性及红细胞内还原型谷胱甘肽（GSH）/氧化型谷胱甘肽（GSSG）比值。具体而言，在通过2小时正常血糖高胰岛素钳夹评估基线胰岛素敏感性后，在1小时内输注谷胱甘肽（1.35 g x m2 x min(-1)）或安慰剂（生理盐水）。按照随机、单盲设计，以1周的间隔交叉重复相同方案。在健康受试者中，基线红细胞内GSH/GSSG比值（P <.0005）和总葡萄糖摄取量（P <.005）显著高于NIDDM患者。在同一受试者中，输注GSH显著增加了总葡萄糖摄取量（从37.1±6.7 μmol kg(-1) x min(-1)增至39.5±7.7 μmol x kg(-1) x min(-1)，P <.05），而输注生理盐水则完全无效。此外，输注GSH后红细胞内GSH/GSSG比值显著增加（从21.0±0.9增至24.7±1.3，P <.05）。在糖尿病患者中也发现了类似的结果，输注GSH后总葡萄糖摄取量（从25.3±9.0 μmol x kg(-1) x min(-1)增至31.4±10.0 μmol x kg(-1) x min(-1)，P <.001）和红细胞内GSH/GSSG比值（从14.8±4.1增至21.7±6.7，P <.01）均显著增加。合并糖尿病患者和对照组的数据后发现，红细胞内GSH/GSSG比值与总葡萄糖摄取量之间存在显著相关性（r =.425，P <.05），GSH输注后相同变量的增加之间也存在显著相关性（r =.518，P <.05）。总之，我们的数据支持以下假设：细胞内GSH氧化还原状态异常在降低NIDDM患者胰岛素敏感性方面起重要作用。因此，静脉输注GSH显著增加了同一患者红细胞内GSH/GSSG比值和总葡萄糖摄取量。
