Effect of Xiaoke Jianpi Decoction(消渴健脾方)on Insulin Resistance in Type 2 Diabetes Mellitus by Regulating PEDF and Activating PI3K/Akt and AMPK Signaling Pathways and Its Possible Mechanism
Objective To explore the effect and possible mechanism of Xiaoke Jianpi Decoction(消渴健脾方)on insulin resistance(IR)in type 2 diabetes mellitus(T2DM)by regulating pigment epithelium-derived factor(PEDF)to activate phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)and adenosine monophosphate-activated protein kinase(AMPK)signaling pathways.Methods 36 experimental rats were randomly divided into 7 groups'control group,type 2 diabetes model group,metformin hydrochloride+T2DM rat group,low-dose Xiaoke Jianpi Decoction group,middle-dose Xiaoke Jianpi Decoction group and high-dose Xiaoke Jianpi Decoction group,with 6 rats in each group.The expression changes of body weight,whole blood glucose,fasting insulin(FINS),liver function,blood lipid,liver glycogen,protein expression levels of p-PI3K,p-Akt,p-GSK-3β,p-AMPK and adipose triglyceride lipase(ATGL),β-actin fluorescence real-time quantitative PCR primers and histopathological changes were compared in different groups.Results After drug intervention,the expressions of ALT,AST,TC,TG and LDL in metformin hydrochloride+T2DM rat group,middle-dose Xiaoke Jianpi Decoction group and low-dose Xiaoke Jianpi Decoction group were significantly lower than those in type 2 diabetes model group,while the expression of HDL-C was significantly higher(P<0.05).FBG,FINS,HbA1c and IR values in metformin hydrochloride+T2DM rat group,middle-dose Xiaoke Jianpi Decoction group and low-dose Xiaoke Jianpi Decoction group were significantly lower than those in type 2 diabetes model group(P<0.05).Compared with the model group of type 2 diabetes mellitus,the contents of hepatic glycogen and PEDF in the rat group of metformin hydrochloride+T2DM,middle-dose Xiaoke Jianpi Decoction group and low-dose Xiaoke Jianpi Decoction group were significantly higher,and the content of PEDF in serum was significantly lower(P<0.05).Compared with metformin hydrochloride+T2DM rat group,the content of hepatic glycogen and PEDF in the high-dose Xiaoke Jianpi Decoction group decreased,while the content of PEDF in serum increased(P<0.05).HE pathological results of he showed that the arrangement of liver hepatocytes in type 2 diabetes model group was disordered,coagulative necrosis,edema and the number of nuclei decreased.The expression levels of PI3K,Akt,GSK-3β,AMPK,ATGL and the level of β-actin fluorescent real-time quantitative PCR primers in the middle-dose Xiaoke Jianpi Decoction group were significantly higher than those in the model group of type 2 diabetes mellitus(P<0.05).Conclusion Middle-dose Xiaoke Jianpi Decoction can decrease the content of liver glycogen and PEDF in liver tissue and increase the content of PEDF in serum by enhancing PI3K/Akt and AMPK signal pathways activated by PEDF in T2DM rats,thus reducing the degree of IR.It is speculated that this is the possible mechanism of lowering blood sugar.