A novel cell model targeted on GLP-1 receptor for application to anti-diabetic candidates screening.
- Author:
Yi HUAN
1
;
Zhu-fang SHEN
Author Information
1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Line;
Cyclic AMP Response Element Modulator;
pharmacology;
Cyclic AMP-Dependent Protein Kinases;
antagonists & inhibitors;
Drug Delivery Systems;
Drug Evaluation, Preclinical;
Genes, Reporter;
Glucagon-Like Peptide-1 Receptor;
Green Fluorescent Proteins;
metabolism;
Hypoglycemic Agents;
agonists;
antagonists & inhibitors;
metabolism;
Islets of Langerhans;
cytology;
drug effects;
metabolism;
Isoquinolines;
pharmacology;
Peptide Fragments;
pharmacology;
Peptides;
antagonists & inhibitors;
pharmacology;
Plasmids;
Rats;
Receptors, Glucagon;
agonists;
antagonists & inhibitors;
genetics;
metabolism;
Recombinant Proteins;
genetics;
metabolism;
Signal Transduction;
Sulfonamides;
pharmacology;
Transfection;
Venoms;
pharmacology
- From:
Acta Pharmaceutica Sinica
2009;44(3):309-313
- CountryChina
- Language:Chinese
-
Abstract:
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.
