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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。
Islet β-cell dedifferentiation is one of the mechanisms leading to its dysfunction. Studies have shown that Fox O1 is closely related to the dedifferentiation of β cells. However, whether high glucose can de-differentiate β cells induced by Fox O1 has not been reported so far. In this study, MIN6 cells were treated with different concentrations of high glucose, β-cell function was detected by glucose-stimulated insulin secretion test (GSIS), real-time fluorescence quantitative PCR and Western blotting, immunofluorescence assay was used to detect β-cell progenitor cell marker gene, β cell marker gene and Fox O1 expression changes. The results showed that the β-cell progenitor cell marker gene expression was significantly increased when the concentration of 35 mmol / L of β-cell was interfered by different concentrations of high glucose. At this concentration, the expression of β-cell marker gene was significantly decreased, the glucose-stimulated insulin secretion of MIN6 cells was decreased and the phosphorylated FoxO1 expression was decreased. These results suggest that high glucose can induce the occurrence of pancreatic β-cell dedifferentiation, the mechanism may be mediated through FoxO1.