高糖通过下调FoxO1磷酸化诱导β细胞去分化  

Down-regulation of FoxO1 Phosphorylation under High Glucose Mediated-De-differentiation of β Cells

作　　者：刘婵[1] 郑晓雅[1] 夏佳佳 任伟[1] 李林蔓[1] 刘兰[1] 

机构地区：[1]重庆医科大学附属第一医院内分泌内科,重庆400016 [2]重庆市长寿区人民医学健康管理科,重庆401220

出　　处：《中国生物化学与分子生物学报》2016年第1期74-79,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：教育部基金项目(No.20135503120001);国家临床重点专科建设项目(2011);重庆市科委自然科学基金面上项目(No.cstc2012jjA 10035)~~

摘　　要：胰岛β细胞发生去分化现象是导致其功能减退的机制之一。已有研究证明,Fox O1与β细胞去分化密切相关。然而,高糖是否可通过Fox O1诱导β细胞发生去分化目前尚未见报告。本研究通过不同浓度高糖干预MIN6细胞,采用葡萄糖刺激胰岛素分泌试验(GSIS)检测β细胞功能;实时荧光定量PCR及蛋白免疫印迹、免疫荧光方法检测高糖干预后β细胞内祖细胞标志基因、β细胞标志基因及Fox O1的表达变化。结果显示,不同浓度高糖干预β细胞后,当浓度达到35 mmol/L时,β细胞祖细胞标志基因表达明显增加。且在该浓度时,检测到β细胞标志基因表达明显降低,MIN6细胞葡萄糖刺激胰岛素分泌功能减退,磷酸化Fox O1表达减少。上述结果提示,高糖可诱导胰岛β细胞去分化的发生,其机制可能是通过Fox O1介导。Recent reports have shown that Fox O1 plays an important role in β cell de-differentiation,which is one of the critical mechanisms underlying pancreatic β cell dysfunction. Whether Fox O1 involves in high glucose-induced β cell de-differentiation remained unknown. In this study,MIN6 cells were exposed in different concentrations of glucose in control group（ 25 mmol / L glucose） and different concentration of glucose groups（ 30,35,40 mmol / L glucose） for 48 hours. Glucose-stimulated insulin secretion（ GSIS） was used to assess the function of treated MIN6 cells. Real-time PCR and Western blot were performed to determine the m RNA and protein expression of progenitor like-cell markers,β cell marker genes,as well as Fox O1. Immunofluorescence was used to detect the expression of Nanog and Pdx-1. The results showed that the expression of progenitor markers increased significantly in the presence of 35 mmol / L glucose,with down-regulated the GSIS and reduced expression of β cell markers and levels of p Fox O1. Our findings suggested that high glucose induced β cell de-differentiation might be mediated by Fox O1.

关 键 词：FOXO1 高糖 β细胞去分化 

分 类 号：R34[医药卫生—基础医学] R58