Effect of glucagon-like peptide-1 agonist on insulin signaling pathway in skeletal muscle of mice with insulin resistance

Abstract

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). 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). 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). Compared with IR group, the expressions of IRC, IRS-1 and PI3K in Ex group were higher(P<0.05). Conclusions Exendin-4 improves insulin resistance by up-regulating the expressions of IRC, IRS-1, and PI3K in the skeletal muscle and promoting the synthesis of muscle glycogen. (Chin J Endocrinol Metab, 2016, 32: 315-320) Key words: Glucagon-like peptide-1 agonist; Insulin resistance; Skeletal muscle; Insulin receptor