ANG-(1-7) IMPROVES ISLET Β CELL FUNCTION BY UP-REGULATING THE ACTIVITY OF ANG-(1-7)-MAS AXIS/PDX-1 

Zeng Zhang, Yanming He, Min Zheng, Zhaohua Fan, Dan Zhang, Yunhao Li, Qiang Zhang, Shasha Yuan, Yanyan Wang, Chenghao Liu, Hongjie Yang^*

Department of Endocrinology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China

Objective: To study the function of islet β cells improved by Ang-(1-7) by up-regulating Ang-(1-7)-Mas axis/PDX-1 activity. 

Methods: Thirty clean-grade male Wistar rats were used. Twelve rats were randomly selected to be the normal control group, and 20 rats were selected and fed a high-fat, high-calorie diet, and the DM rat model was established with 30 mg/kg STZ. Rats with successful modelling were randomly divided into a DM model group (9 rats) and an Ang-(1-7) intervention group (9 rats). The body weight and general condition of rats in each group were observed and recorded. The fasting blood glucose (FBG) of each rat was detected with the glucose oxidase method, and serum insulin and angiotensin II (Ang II) levels were detected with an enzyme-linked immunosorbent assay. The expression level of pancreatic duodenal homeobox factor-1 (PDX-1) protein was detected using Western blotting, and the insulin resistance index (Homa-IR) was calculated. 

Results: The rats in the normal control group showed normal growth and development, good spirit, rapid response and normal body weight. The rats in the model group gradually lost weight, showing polyphagia, polyuria, poor mental function and unresponsiveness. Food consumption of the rats in the intervention group gradually decreased, the number of second stools decreased, and the spirit and reaction rate improved after intervention. Additionally, the body weight and insulin concentration of the model group were significantly lower than those of the control group, and the FBG level was significantly higher than that of the control group (P<0.05). Body weight was not significantly different between the intervention group and the model group (P>0.05). The insulin concentration of the intervention group was significantly higher than that of the model group, and the FBG level was significantly lower than that of the model group (P<0.05). The AngII concentration and Homa-IR value in the model group were significantly higher than those in the control group (P<0.05) and that in the intervention group were significantly lower than those in the model group (P<0.05). The PDX-1 expression level in the model group was significantly lower than that of the control group (P<0.05), but the PDX-1 expression level of the intervention group was significantly higher than that of the control group (P<0.05). 

Conclusion: Ang-(1-7) can improve the function of islet β cells by upregulating the Ang-(1-7)-Mas axis and PDX-1 activity to delay the progression of diabetes.