Effects of cyclosporine A on the expression of phosphorylated AKT in human hepatocytes in vitro and rat hepatocytes in vivo
10.3969/j.issn.1671-7856.2016.06.004
- VernacularTitle:环孢素A对肝细胞中磷酸化AKT蛋白表达的影响
- Author:
Liu YANG
;
Xiaojun LIU
;
Hongyu WANG
;
Yong CAO
;
Yonghua MA
;
Chun XU
- Publication Type:Journal Article
- Keywords:
Cyclosporin A;
Insulin resistance;
Post-transplantation diabetes mellitus;
AKT;
P-AKT
- From:
Chinese Journal of Comparative Medicine
2016;26(6):18-22
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effects of cyclosporin A on the expression of phosphorylated AKT in hepatocytes, and to investigate the mechanism of insulin resistance caused by cyclosporin A. Methods This study included two parts. 1. In vitro experiment:Human hepatocyte HL77022 cell line was cultured at different concentrations of cyclosporin A (0?1 μmol/L, 1 μmol/L, 5 μmol/L) for 48 hours. The expressions of phosphorylated AKT ( P?AKT) in HL77022 cells were measured by Western blot assay. 2. Rat in vivo experiment: SD rats were randomly divided into 2 groups. The rats in the control group were administrated with distilled water 1 mL/Kg/d. The rats in the cyclosporine group were administrated with cyclosporine 25 mg/Kg/d. The total experiment time was 5 months. The levels of fasting blood glucose and insulin were tested at the end of the experiment. The insulin resistance index and insulin sensitivity index were calculated. The expression of P?AKT in the rat hepatocytes was measured by immunohistochemistry. Results 1. Each group of the HL7702 cells treated by CsA ( 0?1 μmol/L, 1 μmol/L, 5 μmol/L ) showed a significantly decreased expression of P?AKT (P<0?05, P<0?01, and P<0?01). 2. After 5 months of therapy, the fasting blood glucose level of rats in the cyclosporine group was 9?28 mmol/L, indicating that cyclosporine?induced diabetic rat models were established. The insulin sensitivity index in the cyclosporine group was lower than that in the control group ( P<0?05 ) . The expression of P?AKT in liver in the cyclosporine group was significantly lower than that in the control group ( P <0?05) . Conclusions Therapeutic dose of cyclosporine has hyperglycemic effects on rats. Cyclosporine can reduce the expression of phosphorylated AKT in hepatic tissue in rats and also decrease the expression of P?AKT in human hepatocyte HL77022 cells, which indicate that cyclosporine may cause insulin resistance by interfering PI3K/AKT signal transduction pathway.
