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

Abstract

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).Methodis 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 12th 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 μg/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 intervention 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 intervention,compared with NGT-group,the 2 h BG in IGT control group and Ex group were higher,the GLUT4 mRNA 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: Glucagon-like peptide-1; Glucose transporter 4; Skeletal muscle