Effects of Zishen pill on hepatic insulin resistance and PI3K-AKT-FOXO1 pathway in KKay mice
Objective To evaluate the hypoglycemic effect of the traditional Chinese medicine decoction Zishen pill on diabetic mice and the mechanism of the drug on hepatic insulin resistance.Methods 21 KKay mice were randomly divided into Zishen pill high-dosage group and Zishen pill low-dosage group,a model group,and 7 C57 mice as the normal group.After continuous administration for 6 weeks,the fasting blood glucose was observed weekly,and the oral glucose tolerance test(OGTT)was performed in the last week of treatment.The enzyme-linked immunosorbent assay(ELISA)was used to detect the fasting insulin(FINS)in the serum of the mice in each group and homeostasis model assessment-insulin resistance(HOMA-IR)was calculated.RT-qPCR was applied to detect the mRNA expression of insulin receptor substrate(IRS),phosphoinositide 3-kinase(PI3K),protein kinase B(PKB/AKT),forkhead box O1(FOXO1),phosphoenolpyruvate carboxykinase(PEPCK),glucose-6-phosphatase(G6pase),glucokinase(GCK).Hematoxylin-eosin staining(HE)and periodic acid Schiff staining(PAS)were used to observe the liver morphology and glycogen distribution.Results Compared with the C group,the FBG,HOMA-IR,and area under curve(AUC)of OGTT in groups H and L decreased significantly,the changes in liver morphology of C group was partially diminished in Zishen pill treated groups,with fewer lipid droplets and more glycogen distribution.The gene expression of FOXO1,PEPCK,and G6pase decreased significantly,and the expression of GCK gene in group H increased significantly.Conclusion The Zishen pill has obvious hypoglycemic effect on KKay mice,and can significantly improve hepatic insulin resistance.The mechanism may be due to its effect of reducing the transcription of FOXO1,PEPCK,G6pase and increase the transcription of GCK,thereby inhibiting gluco-neogenesis and promoting glycogen synthesis.
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维普
