The medicine that functions to maintain the redox state might to the pathological conditions of insulin resistance

细胞外超氧化物歧化酶(EC-SOD)是一种高水平存在于血管壁中的分泌型糖蛋白，可能在血管壁的抗氧化能力中起重要作用。本研究旨在探讨2型糖尿病患者血浆EC-SOD水平及其与胰岛素抵抗的关系。我们测定了122例患者的血浆EC-SOD，首次发现EC-SOD水平与脂联素呈显著正相关，与空腹血糖、体重指数(BMI)、稳态模型评估-胰岛素抵抗指数(HOMA-R)呈显著负相关。19例糖尿病患者给予吡格列酮治疗后，血浆超氧化物歧化酶和脂联素水平明显升高，肿瘤坏死因子-α(TN-α)水平明显下降。目前的观察表明，与胰岛素抵抗发病相关的因素在调节血浆EC-SOD浓度中起重要作用。EC-SOD的表达受多种物质的调节，如细胞因子和血管活性因子。已知的转录因子如CCAAT/增强子结合蛋白(C/EBPs)和过氧化物酶体增殖物激活受体(PPAR)调节与胰岛素抵抗相关的基因。我们发现C/EBPβ增强子催乳素能显著诱导成纤维细胞EC-γ基因和蛋白的表达，而PPAR DNA配体、吡格列酮和其他噻唑烷二酮类药物则不能。对EC-SOD启动子-荧光素酶的缺失分析表明，控制催乳素的一个重要元件位于EC-SOD基因启动子区域的-242~-178之间，其中存在一个已知的C/EBPβ结合位点。通过转录因子配体治疗增加EC-SOD的表达可能是改善胰岛素抵抗病理状态的途径之一。

Extracellular-superoxide dismutase (EC-SOD) is a secretory glycoprotein located in blood vessel walls at high levels and may be important in the antioxidant capability of vascular walls. The aim of this study was to assess plasma levels of EC-SOD and to evaluate the relationship of the EC-SOD level with insulin resistance in type 2 diabetic patients. We determined plasma EC-SOD in 122 patients and found for the first time that the EC-SOD level was strongly and positively related to adiponectin, and significantly and inversely related to fasting plasma glucose, body mass index (BMI) and homeostasis model assessment-insulin resistance index (HOMA-R). Administration of pioglitazone to 19 diabetic patients significantly increased the plasma levels of EC-SOD and adiponectin, while it decreased tumor necrosis factor-α (TNF-α). The present observations suggest that factors related to the pathogenesis of insulin resistance play an important role in the regulation of the plasma EC-SOD concentration.Expression of EC-SOD is known to be regulated by numerous substances such as cytokines and vasoactive factors. Transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptors (PPARs) are known to regulate genes associated with insulin resistance. We found that a C/EBPβ enhancer, prolactin, significantly induced the EC-SOD mRNA and protein levels in cultured fibroblast cell lines, but PPARγ ligands, pioglitazone and other thiazolidinedione agents did not. Deletion analysis of the EC-SOD promoter-luciferase construct showed that an important element responsible for prolactin is located between -242 and -178 in the promoter region of the EC-SOD gene in which a known C/EBPβ-binding site is located. Increasing the EC-SOD expression by treatment with ligands of transcription factors might be one approach to ameliorate the pathological conditions of insulin resistance.