Effect of tacrolimus in the expression of protein p-hosphatase 2A in liver tissue

WANGDeen; CHENChongshu; WANGHongyu; MAYonghua; andXUChun

doi:10.13919/j.issn.2095-6274.2017.02.006

Abstract：Objective This study aimed to establish whether tacrolimus (FK-506) induced diabetes in rats, and analyze the effect of FK-506 on the expression of protein phosphatase 2A (PP2A) in liver tissue of the rats. Methods 40 male SD rats (80-100 g) were randomly divided into FK-506 group and control group. The rats in FK-506 group were administrated with tacrolimus 4 mg/kg daily. The rats in control group were given the same amount of normal drinking water daily. Rat body weights, fasting blood glucose concentration and blood concentration of tacrolimus were measured monthly. After 5 months all rats were euthanized by ether anesthesia. Fasting serum insulin levels of the rats were determined by puncture of cardiac apex, and then homeostasis model assessment-insulin resistance index (HOMA-IR) and insulin secretion index (ISI) were calculated. The expressions of PP2A in liver tissue of the rats were determined by immunohistochemical method. Software of SPSS 17.0 was used for statistical analysis. Results Three months after feeding of FK-506, the average concentration of blood glucose in FK-506 group was (8.07±0.84) mmol/L, in which blood glucose concentrations of 80%of the rats was greater than 7 mmol/L, and were higher as compared with control group (5.27±0.38) mmol/L;blood glucose concentration of all the rats in group FK-506 were greater than 7 mmol/L five months after feeding of FK-506. The HOMA-IR in FK-506 group was significantly higher than in control group (t=47.80, P<0.05) and ISI was significantly lower than the control group (t=37.70, P<0.05). The expression of PP2A in liver tissue in FK-506 group was higher than in control group (χ2=19.80, P<0.05). Conclusions FK-506 can induce diabetes in rats. The expressions of PP2A in liver tissues of diabetic rats induced by FK-506 were increased, which may be due to the hyperglycemic effects of tacrolimus.