Prevention of type 2 diabetes mellitus by selenium compounds

本研究旨在探讨不同硒状态和/或硒化合物摄入对糖尿病发展的影响及其机制。补充亚硒酸钠（Na_2SeO_3）可使2型糖尿病模型NSY小鼠口服糖耐量试验后血糖降低，血浆胰岛素升高。将Na_2SeO_3、甲基亚硒酸和硒- l -蛋氨酸（SeMet）作为葡萄糖耐受的候选药物，应用于链脲佐菌素/烟酰胺诱导的短期糖尿病小鼠模型，结果表明SeMet对葡萄糖耐受最有效。其作用可能与增加胰腺中硒含量和谷胱甘肽过氧化物酶1 (GPX1) mRNA表达，抑制ROS生成，降低血浆游离脂肪酸（FFA）和糖化血红蛋白（HbA1C）水平，增加脂联素水平有关。SeMet通过抑制ROS的产生加速了磷脂酰肌醇-3激酶的激活，这与3T3-L1脂肪细胞中胰岛素受体底物磷酸化的控制有关。棕榈酸酯作为游离脂肪酸处理后Hepa 1-6细胞糖原储存量降低，经SeMet恢复至正常水平。这些结果表明，SeMet通过抑制ROS产生促进脂肪细胞和肝细胞中的胰岛素信号传导，从而改善胰岛素抵抗的作用，因为硒化合物主要增强GPX1在这两个细胞中的表达。

The objective of this study was to investigate the effect and its mechanisms of various selenium status and/or ingestion of selenocompounds on the development of diabetes mellitus. The supplementation of sodium selenite (Na_2SeO_3) resulted in the decrease of blood glucose and the increase of plasma insulin after oral glucose tolerance test in type 2 diabetes model NSY mice. As the possible candidates effective for glucose torelance, Na_2SeO_3, methyl seleninic acid and seleno-L-methionine (SeMet) were administered to streptozotocin/nicotinamide-induced short-term diabetic mouse model, and the results indicated that SeMet was most effective against glucose intolerance. The effect is presumably related to increased selenium content and glutathione peroxidase 1 (GPX1) mRNA expression and suppressed ROS production in pancreas, and decreased free fatty acid (FFA) and HbA1C levels and increased adiponectin level in plasma. SeMet accelerated glucose uptake by phosphatidylinositol-3-kinase activation through the suppression of ROS production that was linked to the control of insulin receptor substrate phosphorylation in 3T3-L1 adipocytes. The glycogen storage lowered by treatment of palmitate as FFA in Hepa 1-6 cells was recovered by SeMet until the normal level. These results suggest that SeMet exhibits the improving effects against insulin resistance by promoting insulin signaling in adipocytes and hepatocytes through the suppression of ROS production because the selenocompound predominantly enhances GPX1 expression in both cells.