天津医药

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重组人胰岛素样生长因子-1对dp/dp小鼠应激性血糖升高的保护作用

孔繁强1,周树民2,赵荣兰3,孙蓓4,梁东春5   

  1. 1. 天津医科大学附属总医院
    2. 天津医科大学第二附属医院
    3. 天津医科大学代谢病医院内分泌研究所
    4. 医科大学代谢病医院
    5. 天津医科大学内分泌研究所
  • 收稿日期:2010-07-30 修回日期:2011-02-14 出版日期:2011-05-15 发布日期:2011-05-15
  • 通讯作者: 梁东春

Protective effect of recombinant human IGF-1 on stress hyperglycemia induced in dp/dp type 2 diabetic mice

  • Received:2010-07-30 Revised:2011-02-14 Published:2011-05-15 Online:2011-05-15

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2013

摘要： 目的：比较重组人胰岛素样生长因子1（rhIGF-1）与胰岛素（Ins）对糖尿病伴有胰岛素抵抗时应激性血糖升高的保护作用。方法：以瘦素受体基因缺陷型dp/dp小鼠为2型糖尿病伴胰岛素抵抗动物模型，电脉冲刺激诱发应激性高血糖。分别给予高剂量胰岛素或rhIGF-1进行干预，观察血糖控制的情况。Real-time PCR及western blot分别检测骨骼肌组织内GluT4基因的表达水平及GLUT4蛋白含量。结果：经电脉冲刺激后，无论是正常小鼠还是dp/dp小鼠均表现出了血糖升高的现象，后者血糖升高的幅度和持续的时间均显著高于正常小鼠。IGF-1可显著性缩短dp/dp小鼠应激性高血糖持续的时间，降低血糖上升的幅度；而胰岛素则未表现出明显的保护作用。定量PCR结果表明，IGF-1可显著增加dp/dp小鼠骨骼肌组织中GluT4基因的表达及GLUT4蛋白在细胞膜中的含量。结论：rhIGF-1对T2DM小鼠被诱发的应激性高血糖具有较胰岛素更好的控制作用，此作用可能是由增加骨骼肌细胞中GLUT4的表达及转位所介导。

关键词: IGF-1, 糖尿病, 应激性高血糖, 葡萄糖转运体4

Abstract: Objective To study, and compare with insulin, the protective effect of rhIGF-1 on stress hyperglycemia induced in dp/dp type 2 diabetic mice. Method Stress hyperglycemia was induced in dp/dp mice by means of electric pulse stimulation. Thereafter, the mice were subjected to the treatment of insulin or rhIGF-1 separately, blood glucose was measured every 30 min after the treatment through three hours. The expression of Glut4 gene in the skeletal muscle was determined by real-time PCR and the amount of GLUT4 molecules on the cell membrane was detected by western blot. Result As a result, rhIGF-1 showed more effective function on controlling stress hyperglycemia than large-dosed insulin and augment Glut4 gene expression as well as GLUT4 cell membrane content in skeletal muscle cells. Conclusion rhIGF-1 had potential therapeutic effect on stress hyperglycemia and this function may be mediated by up-regulating Glut4 expression and promoting GLUT4 membrane translocation in skeletal muscle cells.

Key words: IGF-1, Type 2 diabetic mellitus, stress hyperglycemia, GLUT4