Effects of tacrolimus on the expression of protein phosphatase 2 A and P-AKT in rat hepatocytes
10.3969/j.issn.1005-4847.2016.03.009
- VernacularTitle:他克莫司对大鼠肝脏组织蛋白磷酸酶2A和P-AKT表达的影响
- Author:
Yujian NIU
;
Deen WANG
;
Liu YANG
;
Xinguo CHEN
;
Hongyu WANG
;
Chun XU
- Publication Type:Journal Article
- Keywords:
Post-transplantation diabetes mellitus;
Rat;
Tacrolimus;
P-AKT;
Phosphatase 2A
- From:
Acta Laboratorium Animalis Scientia Sinica
2016;24(3):262-267
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effects of tacrolimus on blood glucose, insulin, expressions of protein phos-phatase 2A and P-AKT in rats in order to explore the mechanism of hyperglycemic action of tacrolimus. Methods Sixty male SD rats (body weight 89. 83 ±4. 44 g) were randomly divided into tacrolimus group (n =40) and control group (n=20). The rats in the tacrolimus group were administrated with tacrolimus 4 mg/kg daily. The rats in the control group were given the same amount of normal drinking water daily. The rat body weight, fasting blood glucose concentration and blood concentration of tacrolimus were measured monthly. All rats were killed at 5 months after the tacrolimus administra-tion. The serum insulin levels were detected by radioimmunoassay method. The expressions of PP2A and P-AKT in liver tissues were assessed by immunohistochemistry. Results After two months of administration, the blood glucose levels in the tacrolimus group were significantly higher than those in the control group. The HOMA-IR in tacrolimus group was signif- icantly higher than that in the control group P<0. 05 ) . ISI was significantly lower than that in the control group ( P<0. 05). Immunohistochemical examination showed that the expression of PP2A in hepatocytes in the tacrolimus group was increased compared with the control group, while expression of P-AKT in hepatocytes of the tacrolimus group was decreased than that in the control group. Conclusions Tacrolimus can induce necrosis of islet cells, decrease of the amount of islet cells and insulin secretion, decease of sensitivity to insulin, and increase the resistance to insulin, therefore, leading to in-crease the blood glucose level in rats. The expression of PP2A in hepatocytes in the tacrolimus group is increased, while the expression of P-AKT is decreased. Interfering of insulin signal transduction pathways may be involved in the hyperglyce-mic effects of tacrolimus.
