重组人胰岛素样生长因子-1对db/db小鼠应激性血糖升高的保护作用

摘要

目的:研究重组人胰岛素样生长因子(rhlGF)-1对2型糖尿病(T2DM)伴胰岛素抵抗(IR)小鼠应激性血糖升高的治疗作用.方法:以瘦素受体基因缺陷型db/db小鼠为动物模型,电脉冲刺激诱发应激性高血糖.给予高剂量胰岛素或rhIGF-1进行干预,观察血糖的变化情况.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:在8周龄时瘦素受体基因缺陷的db/db小鼠表现出了明显的肥胖、高血糖及高胰岛素血症.应激后组间血糖水平的差异有统计学意义(F组间=48.915,P<0.05),组内不同时间点血糖水平差异无统计学意义(F时间=1.295,P>0.05),组间和时间无交互效应(F交互=1.046,P>0.05).采取于预措施后,组间血糖水平差异有统计学意义(F组间=36.947,P<0.05),不同时间点血糖水平差异有统计学意义(F时间=13.880,P<0.05 ),且组间和时间存在交互效应(F交互=ll.769,P<0.05).IGF-1可显著增加db/db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,此作用可能是因骨骼肌细胞中GLUT4的表达及转位增加所致.%Objective: To investigate the therapeutic effects of recombinant human insulin-like growth factor (rhIGF) -1 on stress hyperglycemia in db/db type 2 diabetic mice. Methods: The stress hyperglycemia was induced in db/db mice by means of electric pulse stimulation. Thereafter, the mice were subjected to the treatment of insulin or rhIGF-1 separately. The level of blood glucose was measured . The expression of glucose transporter type 4 (GLUT4) gene in the skeletal muscle was determined by real-time PCR, and the amount of GLUT4 molecules was detected by western blot. Results: Compared with normal control, obesity, hyperglycemia and hyperinsulinemia were found in db/db mice at the age of 8 weeks. After electric pulse stimulation there was a significant difference in the level of blood glucose between db/db mice and control groups (F = 48.915. P ＜ 0.05). However, there was no significant difference in the level of blood glucose in different time points of intra-group (F = 1.295 , P ＞ 0.05). and no interaction between groups and time points (F = 1.046. P ＞ 0.05). After treatments, significantly altemated glycemia can be seen between either different groups (F = 36.947. P ＜ 0.05) or different time points (F = 13.880, P ＜ 0.05). And there was interaction between the variations of group and time point a group-by-time interaction(F = 11.769, P ＜ 0.05). The expression of GLUT4 gene and GLUT4 cell membrane concentration in skeletal muscle cells were significantly increased by IGF-1 in diabetes db/db mice. Conclusion: rhIGF-1 has potential therapeutic effect on stress hyperglycemiae, which may he mediated by up-regulating GLUT4 expression and promoting GLUT4 membrane translocation in skeletal muscle cells of diabetes db/db mice.