Establishment of a novel cell model targeted on FGF-21 receptor for screening anti-diabetic drug candidates.
- Author:
Hong-Mei GAO
1
;
Wen-Fei WANG
;
Qiao ZHANG
;
Yang HAN
;
Qi WANG
;
Gui-Ping REN
;
Yun-Wei FU
;
De-Shan LI
Author Information
1. College of Life Science of Northeast Agricultural University. Harbin 150030, China.
- Publication Type:Journal Article
- MeSH:
3T3-L1 Cells;
Animals;
Drug Evaluation, Preclinical;
Fibroblast Growth Factors;
metabolism;
pharmacology;
Glucose;
metabolism;
Glucose Transporter Type 1;
genetics;
metabolism;
Glucose Transporter Type 4;
genetics;
metabolism;
HEK293 Cells;
Humans;
Hypoglycemic Agents;
metabolism;
Membrane Proteins;
genetics;
metabolism;
Mice;
NIH 3T3 Cells;
Plasmids;
RNA, Messenger;
metabolism;
Receptors, Fibroblast Growth Factor;
agonists;
Recombinant Proteins;
genetics;
metabolism;
Retroviridae;
genetics;
Signal Transduction;
Transfection
- From:
Acta Pharmaceutica Sinica
2011;46(8):904-909
- 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.
