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 胰升血糖素样肽1改善波动性高糖诱导大鼠胰岛细胞增殖功能机制的研究

来自:中国糖尿病杂志  编辑: 张振 李静 苏万江 董一唯 蔡德鸿 张|点击数:|2014-12-16

  糖尿病基础研究

  【摘要】目的 研究胰升血糖素样肽1(GLP-1)对波动性高糖诱导大鼠胰岛细胞增殖功能的影响及机制。 方法 将获取的原代胰岛细胞分为5组,即正常葡萄糖(5.5 mmol/L)组、恒定高糖(30.0 mmol/L)组、波动高糖(每24 h轮换培养于5.5 mmol/L或30.0 mmol/L)组、恒定高糖+GLP-1(100 nmol/L)组和波动高糖+GLP-1(100 nmol/L)组。干预7 d后检测细胞增殖活性、活性氧、细胞周期及周期蛋白cyclinD1、p21、p27、Skp2的表达。 结果 GLP-1干预可降低波动性高糖诱导的细胞内活性氧水平(194.40±19.20),上调促细胞周期cyclinD1、Skp2表达,下调周期抑制蛋白p21、p27表达,使停滞在G0/G1期的细胞比例减少,改善细胞增殖活性(1.38±0.09)(P<0.05)。 结论 GLP-1可通过降低氧化应激水平及对不同细胞周期蛋白表达的调节改善波动性高糖抑制的胰岛细胞增殖活性。

  【关键词】胰升血糖素样肽1;波动性高糖;胰岛细胞;细胞周期;细胞增殖

  【Abstract】Objective To investigate the effect of GLP-1 on the proliferative activity in pancreatic cells treated with intermittent high glucose and the potential mechanism. Methods Pancreatic cells from Wistar rats were treated respectively with normal glucose (5.5 mmol/L), constant high glucose (30.0 mmol/L) and intermittent high glucose (rotation per 24 h in 5.5 or 30.0 mmol/L) in the presence or absence of GLP-1 (100 nmol/L) for 7 d. Proliferative activity, intracellular reactive oxygen species (ROS), cell cycle and expression of cyclinD1, p21, p27, Skp2 were determined. Results Treatment of GLP-1 significantly decreased ROS level(194.40±19.20)(P<0.05) induced by intermittent high glucose, increased the expression of cyclinD1 and Skp2, decreased the expression of p7 and p21 (P<0.05). Then significantly decreased the cell proportion in G0/G1 phase and finally increased the cell proliferation activity (1.38±0.09)(P<0.05). Conclusion GLP-1 decreased the intracellular ROS level and regulating expressions of protein. And finally promote the cell cycle progression and proliferation activity.

  【Key words】 Glucagon-like peptide-1 (GLP-1);Intermittent high glucose;Pancreatic cells;Cell cycle;Cell proliferation

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