Effect of glucagon-like peptide-1 agonist on insulin signaling pathway in skeletal muscle of mice with insulin resistance
10.3760/cma.j.issn.1000-6699.2016.04.014
- VernacularTitle:胰升糖素样肽1受体激动剂对胰岛素抵抗小鼠骨骼肌胰岛素信号通路的影响
- Author:
Xiaoyi XU
;
Jing LI
;
Ling GAO
;
Min XIE
;
Zheng LI
- Publication Type:Journal Article
- Keywords:
Glucagon-like peptide-1 agonist;
Insulin resistance;
Skeletal muscle;
Insulin receptor
- From:
Chinese Journal of Endocrinology and Metabolism
2016;32(4):315-320
- CountryChina
- Language:Chinese
-
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, 3μg·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 insulinreceptor(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 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.
