高糖通过下调FoxO1磷酸化诱导β细胞去分化

发布时间：2018-10-24 16:46

【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。
[Abstract]:The dedifferentiation of islet 尾 cells is one of the mechanisms leading to the decline of islet function. It has been shown that Fox O 1 is closely related to 尾-cell dedifferentiation. However, whether high glucose can induce 尾-cell dedifferentiation through Fox O 1 has not been reported. In this study, MIN6 cells were treated with different concentrations of high glucose, and 尾 -cell function was detected by glucose-stimulated insulin secretion test (GSIS), real-time fluorescence quantitative PCR and Western blot. The expression of 尾 -cell marker gene, 尾 -cell marker gene and Fox O _ 1 were detected by immunofluorescence. The results showed that when the concentration of high glucose was 35 mmol/L, the expression of marker gene of 尾 -cell progenitor cells increased significantly. At this concentration, 尾 -cell marker gene expression was significantly decreased, glucose-stimulated insulin secretion was decreased and phosphorylated Fox O1 expression was decreased in MIN6 cells. These results suggest that high glucose can induce the dedifferentiation of islet 尾 cells, which may be mediated by Fox O 1.
【作者单位】：重庆医科大学附属第一医院内分泌内科;重庆市长寿区人民医学健康管理科;
【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)~~
【分类号】：R587.1

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