Establishment of a novel cell model targeted on FGF-21 receptor for screening anti-diabetic drug candidates.
- Author:
Hongmei GAO
;
Wenfei WANG
;
Qiao ZHANG
;
Yang HAN
;
Qi WANG
;
Guiping REN
;
Yunwei FU
;
Deshan LI
- Publication Type:Journal Article
- From:
Acta Pharmaceutica Sinica
2011;46(8):904-9
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this project is to establish a fibroblast growth factor-21 (FGF-21) signaling pathway targeted cell model, for screening a class of FGF-21 receptor agonists as anti-diabetic candidates. FGF-21 requires beta klotho transmembrane proteins as co-receptor for the activation of tyrosine kinase FGF receptor (FGFR) signaling, thereby activating a series of intracellular signaling pathways and regulating gene transcription for glucose metabolism. Firstly a recombinant plasmid expressing co-receptor beta klotho and EGFP reporter genes was constructed. After introducing the recombinant plasmid into package cells, the cell culture supernatant was used to infect 3T3-L1 cells, which were then screened for stably expressing beta klotho gene. Administration of FGF-21 increased the expression of GLUT1 and stimulated GLUT1-mediated glucose uptake. This novel cell model can be conveniently used in high-throughput drug screening of FGF-21 or FGF-21 analogues.
