艾塞那肽对糖耐量减低大鼠骨骼肌葡萄糖转运蛋白4表达的作用

目的探讨胰高血糖素样肽．1（glucagon—like peptide-1，GLP-1）受体激动剂艾塞那肽对糖耐量减低（impaired glucose tolerance, IGT）大鼠骨骼肌葡萄糖转运蛋白4（glucose transporter 4, GLUT4）表达的作用。方法54只Wistar大鼠，按照完全随机化分组方法分为正常糖耐量组（NGT组，18只）和IGT组（36只），NGT组予常规饲料，IGT组予高糖高脂饲料。12周时IGT造模成功，成模后从IGT组随机抽取18只大鼠设为艾塞那肽干预组（Ex组），每日2次皮下注射艾塞那肽（5μg／kg）；另外18只设为IGT对照组。NGT组及IGT对照组均给予等体积生理盐水皮下注射。于干预前和干预后4周分别测空腹血糖（fasting blood glucose，FBG）和餐后2h血糖（2hBG）；实时荧光定量PCR检测骨骼肌GLUT4mRNA的表达，免疫组织化学法检测骨骼肌GLUT4蛋白的表达。各组间两两比较采用单因素方差分析（ANOVA），LSD—t检验。结果干预前，与NGT组比较，IGT对照组及Ex组2hBG增高，骨骼肌GLUT4mRNA表达降低，差异有统计学意义（均P〈0．05）。IGT对照组及Ex组骨骼肌细胞内棕黄色着色较少，NGT组着色广泛，着色颗粒较多。艾塞那肽干预4周后，与同期IGT对照组及干预前Ex组比较，Ex组2hBG下降，骨骼肌GLUT4mRNA表达增高，差异均有统计学意义（P〈0．05）。干预后Ex组较同期IGT对照组及干预前Ex组骨骼肌细胞内棕黄色着色增多，主要表达在细胞浆中。结论艾塞那肽可上调骨骼肌GLUT4的表达。促进骨骼肌葡萄糖的摄取，降低餐后血糖。

Effect of glucagon-like peptide-1 agonist on expression of glucose transporter 4 in the skeletal muscle of rats with impaired glucose tolerance

Objective To investigate the effect of glucagon-like peptide-1 agonist （exendin-4） on expression of glucose transporter 4 （GLUT4） in the skeletal muscle of rats with impaired glucose tolerance （IGT）. Methods 54 Wistar rats were randomly assigned into normal glucose tolerance group （ NGT group, n = 18） and impaired glucose tolerance group（ IGT group, n = 36）. The rats in NGT group were fed with routine diet and the rats in IGT group were fed with high-sugar high-fat diet. At the 12＇h week, IGT models were tested successful. Then, half of the rats were allocated to intervention group （Ex group） and the rest were set as IGT control group. The rats in Ex group were subject to exendin-4 subcutaneous injection （5 Izg/kg, twice daily）. Each rat in NGT group and IGT control group was given the same volume of saline as injection. FBG and 2 h BG were measured before inter- vention and after 4 weeks. The expression of GLUT4 mRNA and GLUT4 in the skeletal muscle were respectively measured by real time quantitative polymerase chain reaction and immunohistochemistry. Inter-group comparison was conducted using analysis of variance （ANOVA） and least square deviation-test （LSD-t）. Results Before in- tervention, compared with NGT-group, the 2 h BG in IGT control group and Ex group were higher, the GLUT4 mR- NA of skeletal muscle in IGT control group and Ex group were lower （respectively P 〈 0. 05）. The skeletal muscle cells in IGT control group and Ex group were less colored while the skeletal muscle cells in NGT group were colored extensively, and more colored granules. After 4 weeks of exendin-4 intervention, compared with IGT control group and Ex group of non-intervention, the 2 h BG level in Ex group was lower and the expression level of GLUT4 mRNA of skeletal muscle was higher （ respectively P 〈 0. 05 ）. After intervened with exendin-4 for 4 weeks,the GLU protein mainly expressed in cytoplasma of skeletal muscle cells. Its expression was higher in Ex group than in IGT group and in Ex group before intervention. Conclusion Exendin-4 may up-regulate the expression of GLUT4, increase glucose intake of the skeletal muscle, and reduce postprandial blood sugar. [ Key Words ]