Liraglutide Exerts Antidiabetic Effect via PTP1B and PI3K/Akt2 Signaling Pathway in Skeletal Muscle of KKAy Mice.
Liraglutide Exerts Antidiabetic Effect via PTP1B and PI3K/Akt2 Signaling Pathway in Skeletal Muscle of KKAy Mice.
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DOI：
10.1155/2014/312452
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发表时间：
2014
影响因子：
2.8
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Ji W;Chen X;Lv J;Wang M;Ren S;Yuan B;Wang B;Chen L
背景。利拉鲁肽（一种胰高血糖素样肽1类似物）用于治疗可产生葡萄糖依赖性胰岛素分泌的2型糖尿病（T2DM）。的目标。目的是探讨利拉鲁肽是否能改善糖尿病KKAy小鼠骨骼肌肌原纤维和线粒体损伤及其机制。方法。将雄性KKAy小鼠分为2组：利拉鲁肽组（利拉鲁肽皮下注射250 μg/kg/d）和模型组；同时以雄性C57BL/6J小鼠为对照。6周后，电镜观察骨骼肌超微结构。实时荧光定量PCR检测蛋白酪氨酸磷酸酶1B （PTP1B）、磷脂酰肌醇3-激酶（PI3K）和葡萄糖转运蛋白4 （GLUT4）的基因表达。Western blot检测上述分子及磷酸化akt2 （p-Akt2）蛋白水平。结果。利拉鲁肽可使KKAy小鼠骨骼肌线粒体数量（+441%）、线粒体面积（+113%）和线粒体面积/100µm2（+396%）增加，显著改善线粒体损伤。real-time PCR和Western blot结果显示，利拉鲁肽下调PTP1B，上调PI3K和GLUT4 （P < 0.01）。P -Akt2/Akt2蛋白水平升高（P < 0.01）。结论。这些结果表明利拉鲁肽可通过PTP1B和PI3K/Akt2信号通路改善骨骼肌肌原纤维和线粒体损伤。
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 µm2 (+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.