title: Liraglutide Exerts Antidiabetic Effect via PTP1B and PI3K/Akt2 Signaling Pathway in Skeletal Muscle of KKAy Mice.
abstract: Background. Liraglutide (a glucagon-like peptide 1 analog) was used for the treatment of type 2 diabetes (T2DM) which could produce glucose-dependent insulin secretion. Aim. The aim was to investigate whether liraglutide could improve myofibril and mitochondria injury in skeletal muscle and the mechanisms in diabetic KKAy mice. Method. We divided the male KKAy mice into 2 groups: liraglutide group (250 μg/kg/day liraglutide subcutaneous injection) and model group; meanwhile, the male C57BL/6J mice were considered as the control. After 6 weeks, the ultrastructure of skeletal muscle was observed by electron microscope. The gene expressions of protein tyrosine phosphatase 1B (PTP1B), phosphatidylinositol 3-kinase (PI3K), and glucose transporter type 4 (GLUT4) were determined by real-time PCR. The protein levels of the above molecules and phospho-Akt2 (p-Akt2) were measured by Western blot. Results. Liraglutide significantly ameliorated the injury of mitochondria by increasing the number (+441%) and the area (+113%) of mitochondria and mitochondrial area/100 µm(2) (+396%) in skeletal muscle of KKAy mice. The results of real-time PCR and Western blot showed that liraglutide downregulated PTP1B while it upregulated PI3K and GLUT4 (P < 0.01). The protein level of p-Akt2/Akt2 was also increased (P < 0.01). Conclusion. These results revealed that liraglutide could improve myofibril and mitochondria injury in skeletal muscle against T2DM via PTP1B and PI3K/Akt2 signaling pathway.
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ji
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Xi'an No. 1 Hospital, Xi'an, Shaanxi 710002, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lv
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Ren
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Bingxiang
authors.initials: B
authors.lastname: Yuan
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Chen