Abstract: AIM: To investigate the expression of glucose metabolism genes associated with tacrolimus-induced post-transplant diabetes in the mouse kidney and the mechanisms involved in the regulation of glucose metabolism by farnesylate X (FXR) receptor activator.  METHODS: The gene expression levels of FXR, small heterodimeric partner-1 (SHP-1), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter protein-2 (GLUT2) were measured after 72 h in HK-2 cell lines treated with tacrolimus and tacrolimus+FXR agonist (GW4064) and control groups, respectively. C57BL/6J male mice were gavaged with tacrolimus and tacrolimus+FXR agonist for 12 weeks, respectively, and the control group was given saline to observe the changes in body weight and blood glucose; after the animals were treated, the gene expression levels of FXR, SHP-1, PEPCK, and GLUT2 were detected, respectively. RESULTS: In cellular experiments, the expression of FXR, SHP-1 and GLUT2 genes was decreased in the tacrolimus-treated group (P<0.05) and the expression of the PEPCK gene was significantly upregulated compared with the control group (P<0.05). In animal experiments, compared with the control group, the blood glucose values were significantly increased in the tacrolimus-treated group and significantly decreased in the tacrolimus+FXR agonist combination intervention group (P<0.05), and the expression of FXR, SHP-1 and GLUT2 genes were upregulated (P<0.05) and the expression of PEPCK genes was significantly decreased in the mice kidney (P<0.05).CONCLUSION: FXR agonists can improve tacrolimus-induced abnormal glucose metabolism after transplantation. Therefore, FXR may be a potential new target for the prevention and treatment of post-transplant diabetes.

Key words: farnesoid X receptor, post-transplant diabetes, gluconeogenesis