FXR agonist GW4064 ameliorates tacrolimus-induced abnormalities in glucose metabolism
10.12092/j.issn.1009-2501.2022.04.018
- Author:
Hao LI
1
;
Ling LI
1
;
Zhiping XIA
1
;
Qifa YE
1
;
Guizhu PENG
1
;
Qifa YE
2
Author Information
1. Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation
2. The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology
- Publication Type:Journal Article
- Keywords:
Farnesoid X receptor;
Gluconeogenesis;
Post-transplant diabetes
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2022;27(4):466-472
- CountryChina
- Language:Chinese
-
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.
