Prevention of type 2 diabetes mellitus by selenium compounds

硒化合物预防2型糖尿病

• 批准号: 20590128
• 负责人: UENO Hitoshi
• 金额: $ 2.75万
• 依托单位: Setsunan University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590128/
• 关键词: セレン; 糖尿病; インスリン; 耐糖能; 酸化ストレス; セレノメチオニン; 脂肪細胞; 3T3-L1; 血糖値; ストレプトゾトシン; ニコチンアミド; 亜セレン酸; 酸化的ストレス; グルタチオン

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.

本研究的目的是探讨不同硒状态和/或摄入硒化合物对糖尿病发生的影响及其机制。补充亚硒酸钠（Na_2SeO_3）可使2型糖尿病模型NSY小鼠口服葡萄糖耐量试验后血糖降低，血浆胰岛素升高。以链脲佐菌素/烟酰胺诱导的短期糖尿病小鼠模型为模型，分别给予Na_2SeO_3、甲基亚硒酸和硒代甲硫氨酸（SeMet），结果表明SeMet对糖耐量异常有较好的抑制作用。其作用可能与硒含量增加、谷胱甘肽过氧化物酶1（GPX 1）mRNA表达增加、胰腺ROS生成抑制、血浆游离脂肪酸（FFA）和HbA 1C水平降低、脂联素水平升高有关。SeMet通过抑制ROS的产生来加速磷脂酰肌醇-3-激酶激活的葡萄糖摄取，ROS的产生与3 T3-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FFA处理Hepa 1-6细胞降低的糖原储存被SeMet恢复至正常水平。这些结果表明，硒代蛋氨酸通过抑制ROS的产生，促进脂肪细胞和肝细胞中的胰岛素信号传导，表现出改善胰岛素抵抗的效果，因为硒代化合物主要增强GPX 1在两种细胞中的表达。

项目成果

セレノメチオニンの短期糖尿病マウスモデルに対するインスリン様作用

硒代蛋氨酸对短期糖尿病小鼠模型的胰岛素样作用

• 发表时间: 2009
• 作者: 上野仁;清水良;原義浩;奥野智史;坂崎文俊;中室克彦
• 通讯作者: 中室克彦

Effect of sodium selenite supplementation on glucose intolerance and pancreatic oxidative stress in type 2 diabetic mice under different selenium status

补充亚硒酸钠对不同硒状态下2型糖尿病小鼠糖耐受不良和胰腺氧化应激的影响

• 发表时间: 2009
• 期刊: Journal of Health Science
• 作者: Ryo Shimizu;Hitoshi Ueno;Tomofumi Okuno;Fumitoshi Sakazaki;Katsuhiko Nakamuro
• 通讯作者: Katsuhiko Nakamuro

セレノメチオニンのインスリン抵抗性改善作用とその機序

硒代蛋氨酸改善胰岛素抵抗的作用及其机制

• 发表时间: 2011
• 作者: 原義浩;家次真優美;清水良;荒川友博;坂崎文俊;奥野智史;上野仁
• 通讯作者: 上野仁

セレンの糖尿病マウスモデルに対するinsulin様作用

硒对糖尿病小鼠模型的胰岛素样作用

• 发表时间: 2008
• 作者: 上野仁;清水良;奥野智史;坂崎文俊;中室克彦
• 通讯作者: 中室克彦

Difference in glucose intolerance between C57BL/6J and ICR strain mice with streptozotocin/nicotinamide-induced diabetes

• DOI: 10.2220/biomedres.33.63
• 发表时间: 2012-02-01
• 期刊: BIOMEDICAL RESEARCH-TOKYO
• 影响因子: 1.2
• 作者: Shimizu, Ryo;Sakazaki, Fumitoshi;Ueno, Hitoshi
• 通讯作者: Ueno, Hitoshi