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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Animals
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Drug Evaluation, Preclinical
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Fibroblast Growth Factors / metabolism
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Fibroblast Growth Factors / pharmacology*
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Glucose / metabolism
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Glucose Transporter Type 1 / genetics
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Glucose Transporter Type 1 / metabolism
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Glucose Transporter Type 4 / genetics
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Glucose Transporter Type 4 / metabolism
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HEK293 Cells
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Humans
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Hypoglycemic Agents / metabolism*
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Klotho Proteins
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Mice
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NIH 3T3 Cells
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Plasmids
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RNA, Messenger / metabolism
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Receptors, Fibroblast Growth Factor / agonists*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Retroviridae / genetics
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Signal Transduction
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Transfection
Substances
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Glucose Transporter Type 1
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Glucose Transporter Type 4
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Hypoglycemic Agents
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KLB protein, human
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Membrane Proteins
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RNA, Messenger
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Receptors, Fibroblast Growth Factor
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Recombinant Proteins
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fibroblast growth factor 21
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fibroblast growth factor-21 receptor, mouse
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Fibroblast Growth Factors
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Klotho Proteins
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Glucose