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的硒状态和/或硒化合物的摄入对糖尿病发生的影响及其机制。补充亚硒酸钠(Na_2SeO_3)导致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。作为可能对葡萄糖耐量有效的候选药物，Na_2SeO_3、甲基硒酸和硒代-L-蛋氨酸（SeMet）被给予链脲佐菌素/烟酰胺诱导的短期糖尿病小鼠模型，结果表明SeMet对葡萄糖耐量最有效。这种效应可能与增加硒含量和谷胱甘肽过氧化物酶 1 (GPX1) mRNA 表达、抑制胰腺中 ROS 产生、降低血浆中游离脂肪酸 (FFA) 和 HbA1C 水平以及增加脂联素水平有关。 SeMet 通过抑制 ROS 的产生，通过激活磷脂酰肌醇 3 激酶来加速葡萄糖的摄取，而 ROS 的产生与 3T3-L1 脂肪细胞中胰岛素受体底物磷酸化的控制有关。在 Hepa 1-6 细胞中，通过以 FFA 形式处理棕榈酸酯而降低的糖原储存可通过 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，从而表现出改善胰岛素抵抗的作用，因为硒化合物主要增强这两种细胞中 GPX1 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

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

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

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

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