中文摘要：

目的研究胰升糖素样肽1受体激动剂艾塞那肽对胰岛素抵抗（IR）小鼠骨骼肌胰岛素信号通路的影响。方法将30只KM小鼠分为正常对照组（NC组，n=10）及IR组（n=20），NC组喂以常规饲料，IR组喂以高脂饲料16周。IR造模成功后，从IR组抽取10只小鼠以艾塞那肽（Ex组，3μg·kg^-1·d^-1）干预4周，NC组及IR组均给予等剂量的生理盐水。于干预前后分别测体重、空腹血糖（FBG）和空腹胰岛素（FINS），并计算稳态模型评估的胰岛素抵抗指数（HOMA．IR）；过碘酸雪夫染色（PAS染色）观察骨骼肌糖原含量的变化，Western印迹法及免疫组织化学法检测骨骼肌胰岛素受体（IRC）、胰岛素受体底物-1（IRS-1）及磷脂酰肌醇3激酶（P13K）蛋白的表达。结果干预前，与Nc组比较，IR组及Ex组小鼠体重、FBG及HOMA-IR增高（均P〈0．05），FINS增高不明显（P〉0．05）。干预后与干预前相比，3组小鼠体重均增加，但IR组增加最为显著。干预后，与同期IR组及干预前Ex组比较，Ex组小鼠FBG及HOMA-IR降低（均P〈0．05），FINS降低不明显（P〉0．05）；PAS染色显示Nc组骨骼肌细胞内紫红色着色广泛，着色颗粒较多，IR组着色较少。Ex组介于两者之间；与NC组相比，IR组骨骼肌中IRC、IRS-1及P13K的表达显著降低（P〈0．05），Ex组无明显降低（P〉0．05）；与IR组相比，Ex组骨骼肌中IRC、IRS-1及PDK的表达增加（P〈0．05）。结论艾塞那肽通过上调骨骼肌IRC、IRS-1及P13K的表达，促进骨骼肌糖原合成，改善骨骼肌IR。

英文摘要：

Objective To study the effect of glucagon-like peptide-1 agonist （exendin-4） on insulin signaling pathway in skeletal muscle of mice with insulin resistance （IR）. Methods Thirty male KM mice were divided into normal control group （ NC group, n = 10 ） and IR group （ n = 20）. The mice in NC group and IR group were fed with routine diet and high-fat diet for 16 weeks, respectively. After IR models were successfully established, 10 mice in IR group were treated with exendin-4 （Ex group, 3 μg · kg^-1 · d^-1 ）for 4 weeks. NC group and IR group were given the same dose of normal saline. Body weight, fasting blood glucose （ FBG）, and fasting insulin （FINS） were measured before and after the intervention, and homeostasis model assessment for insulin resistance （ HOMA-IR ） was calculated. The muscle glycogen content were measured by Periodic Acid-Schiff Stain （PAS）. The expressions of insulin receptor （ IRC ）, insulin receptor substrate-1 （ IRS-1 ）, and phosphatidylinositol 3-kinase （PI3K） in the skeletal muscle were measured by Western blot and immunohistochemistry. Results Before intervention, the body weight, FBG, and HOMA-IR of IR group and Ex group were higher compared with NC group （ all P〈0. 05 ）, but FINS did not rise significantly （ P 〉 0.05 ）. Compared with before intervention, the body weight of three groups after intervention were all increased, but increased more significantly in the IR group. After intervention, the FBG and HOMA-IR in Ex group decreased, compared with IR group and Ex group of non-intervention （ all P〈0.05 ）, but FINS did not decrease significantly（ P〉0.05 ）. The skeletal muscle cells in NC control were colored extensively and more colored granules, while IR group were less colored, and Ex group were between NC group and IR group. Compared with NC group, the expressions of IRC, IRS-1, and PI3K in the skeletal muscle of IR group were significantly decreased （ P〈0. 05 ）, not in Ex group （ P〉0. 05 ）. Compared w