A novel cell model targeted on GLP-1 receptor for application to anti-diabetic candidates screening

The aim of this project is to establish a GLP-1 signaling pathway targeted cell model, for screening the new class of GLP-1 receptor agonists as anti-diabetic candidates.  Firstly construct a recombined plasmid with multi-copied specific response element (RIP-CRE) regulated by GLP-1 signaling pathway and E-GFP    reporter gene.  Transient transfect this recombined plasmid into islet cell NIT-1, then detect the responsibility of transfected cell to GLP-1 analogue, Exendin 4.  For secondly, use stable transfection and monocloning cell  culture to obtain a GLP-1 signaling-specific cell line.  It indicates that this cell model can response to Exendin 4, which response can be completely inhibited by GLP-1 receptor antagonist, Exendin 9-39, further showing GLP-1 receptor specific activity with a cAMP-PKA-independently mechanism.  Establishment of this novel cell model can be used in high-throughput drug screening of peptides or small molecular GLP-1 analogues.