Diaz-Morales Noelia, Rovira-Llopis Susana, Bañuls Celia, Lopez-Domenech Sandra, Escribano-Lopez Irene, Veses Silvia, Jover Ana, Rocha Milagros, Hernandez-Mijares Antonio, Victor Victor M
1 Service of Endocrinology and Nutrition, University Hospital Doctor Peset , Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain .
2 CIBERehd-Department of Pharmacology, University of Valencia , Valencia, Spain .
Antioxid Redox Signal. 2017 Dec 10;27(17):1439-1445. doi: 10.1089/ars.2017.7122. Epub 2017 Jun 2.
Since metformin can exert beneficial vascular effects, we aimed at studying its effect on reactive oxygen species (ROS) production, antioxidant enzyme expression, levels of adhesion molecules, and leukocyte-endothelium interactions in the leukocytes from type 2 diabetic (T2D) patients. The study was carried out in 72 T2D patients (41 of whom were treated with metformin for at least 12 months at a dose of 1700 mg per day), and in 40 sex- and age-matched control subjects. Leukocytes from T2D patients exhibited enhanced levels of mitochondrial ROS and decreased mRNA levels of glutathione peroxidase 1 (gpx1) and sirtuin 3 (sirt3) with respect to controls, whereas metformin was shown to revert these effects. No changes were observed on total ROS production and the expression levels of superoxide dismutase 1 and catalase. Furthermore, increases in leukocyte-endothelial interactions and intercellular adhesion molecule-1 and P-selectin levels were found in T2D and were also restored in metformin-treated patients. Our findings raise the question of whether metformin could modulate the appearance of atherosclerosis in T2D patients and reduce vascular events by decreasing leukocyte oxidative stress through an increase in gpx1 and sirt3 expression, and undermining adhesion molecule levels and leukocyte-endothelium interactions. Antioxid. Redox Signal. 27, 1439-1445.
由于二甲双胍可发挥有益的血管效应，我们旨在研究其对2型糖尿病（T2D）患者白细胞中活性氧（ROS）生成、抗氧化酶表达、黏附分子水平以及白细胞与内皮细胞相互作用的影响。该研究纳入了72例T2D患者（其中41例接受二甲双胍治疗，剂量为每日1700毫克，至少治疗12个月），以及40例年龄和性别匹配的对照受试者。与对照组相比，T2D患者的白细胞中线粒体ROS水平升高，谷胱甘肽过氧化物酶1（gpx1）和沉默调节蛋白3（sirt3）的mRNA水平降低，而二甲双胍可逆转这些效应。总ROS生成以及超氧化物歧化酶1和过氧化氢酶的表达水平未观察到变化。此外，在T2D患者中发现白细胞与内皮细胞的相互作用以及细胞间黏附分子-1和P-选择素水平增加，而在接受二甲双胍治疗的患者中这些指标也恢复正常。我们的研究结果提出了一个问题，即二甲双胍是否可以通过增加gpx1和sirt3的表达、降低黏附分子水平以及减少白细胞与内皮细胞的相互作用，来减轻白细胞氧化应激，从而调节T2D患者动脉粥样硬化的发生并减少血管事件。《抗氧化与氧化还原信号》27卷，第1439 - 1445页 。
