Department of Internal Medicine I, Regensburg University Hospital, D-93042 Regensburg, Germany.
Exp Mol Pathol. 2011 Feb;90(1):101-6. doi: 10.1016/j.yexmp.2010.10.010. Epub 2010 Oct 28.
Type 2 diabetes (T2D) is characterized by increased oxidative stress contributing to the development of cardiovascular disease (CVD). Monocytes are critically important in the pathogenesis of CVD and antioxidant enzymes like superoxide dismutase (SOD2) protect these cells from excessive reactive oxygen species (ROS). Adiponectin is an adipocyte-derived protein with atheroprotective function and the effect of adiponectin on monocyte SOD2 was analyzed herein. Adiponectin upregulated SOD2 mRNA and dose- and time-dependently induced SOD2 protein in primary human monocytes. Elevated systemic free fatty acids (FFA) are commonly found in T2D patients and palmitic acid as well as oleic acid reduced monocyte SOD2 protein. Adiponectin mediated upregulation of SOD2, however, was not affected by FFA incubation. SOD2 protein was reduced in T2D monocytes compared to monocytes of age- and body mass index-matched healthy controls. Adiponectin still induced SOD2 in T2D monocytes but efficiency tended to be reduced. In summary this study indicates that elevated systemic free fatty acids and impaired adiponectin activity contribute to reduced SOD2 and most likely increased oxidative stress in T2D monocytes.
2 型糖尿病（T2D）的特征是氧化应激增加，导致心血管疾病（CVD）的发生。单核细胞在 CVD 的发病机制中至关重要，而超氧化物歧化酶（SOD2）等抗氧化酶可以保护这些细胞免受过度的活性氧（ROS）的侵害。脂联素是一种脂肪细胞衍生的蛋白，具有抗动脉粥样硬化的功能，本文分析了脂联素对单核细胞 SOD2 的作用。脂联素可上调原代人单核细胞的 SOD2 mRNA，并呈剂量和时间依赖性诱导 SOD2 蛋白。T2D 患者常伴有全身性游离脂肪酸（FFA）升高，棕榈酸和油酸均可降低单核细胞 SOD2 蛋白。然而，FFA 孵育并不影响脂联素介导的 SOD2 上调。与年龄和体重指数匹配的健康对照者的单核细胞相比，T2D 患者的单核细胞 SOD2 蛋白减少。脂联素仍能诱导 T2D 单核细胞产生 SOD2，但效率趋于降低。综上所述，本研究表明，全身性游离脂肪酸升高和脂联素活性受损导致 T2D 单核细胞 SOD2 减少，很可能导致氧化应激增加。
