山柰酚对2型糖尿病小鼠骨骼肌PI3K-AKT-GLUT4信号通路的影响

Effects of Kaempferol on the Skeletal Muscle of KKAy Mice via PI3K-AKT-GLUT4 Signaling

目的:探讨山柰酚对KKAy小鼠骨骼肌PI3K/AKT/GLUT4信号通路的影响。方法:以自发型2型糖尿病KKAy小鼠为动物模型,通过对糖尿病小鼠进行为期6周的山柰酚灌胃给药治疗,利用生化、免疫组织化学及免疫印迹法等检验方法,检测PI3K-AKT-GLUT4信号通路重要靶点的表达,探讨山柰酚改善糖尿病KKAy小鼠骨骼肌胰岛素敏感性及对胰岛素信号转导通路PI3K-AKT-GLUT4的影响。结果:山柰酚具有显著降低KKAy小鼠体重、空腹血糖、随机血糖的作用,ITT实验结果说明:山柰酚能够显著降低胰岛素注射30 min时的血糖,显著降低ITT曲线下面积,改善胰岛素抵抗。此外,山柰酚能够显著上调KKAy小鼠骨骼肌PI3K、AKT、GLUT4基因的表达,能够上调AKT、GLUT4蛋白的表达。结论:山柰酚具有显著降低KKAy小鼠血糖、体重的作用,能够改善胰岛素抵抗,其作用机制可能与上调骨骼肌PI3K-AKT-GLUT4信号通路有关。

This study aimed to investigate the effects of kaempferol on the skeletal muscle of KKAy mice via PI3K-AKT-GLUT4 signaling.Spontaneous type 2 diabetic KKAy mice were made up for the model group.After 6-week treatment of kaempferol by intragastric administration,key targets of PI3K-AKT-GLUT4 signaling were detected using biochemical and immunohistochemical technique,and western blot.It was found that the body weight,fast blood glucose and random blood glucose were decreased after kaempferol administration.ITT results show that blood glucose at 30 min after injecting insulin and the area under the curve drop were reduced in the kaempferol group,and so was the insulin resistance index in the kaempferol group.In addition,the m RNA expressions of PI3 K,AKT and GLUT4 in the kaempferol group increased significantly,while the protein levels of AKT and GLUT4 were up-regulated by kaempferol administration.It was concluded that kaempferol can significantly regulate the blood glucose,body weight and insulin resistance in mice through activating the PI3K-AKT-GLUT4 signaling.