Establishment of a novel cell model targeted on FGF-21 receptor for screening anti-diabetic drug candidates

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 β 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 β 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 β 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.