Abstract: Using the technique of phage screening, we utilized the glucagonlike peptide1 receptor (GLP-1R) of RINm5F cell as the target to screen GLP-1 receptor agonists through competitive elution by Exendin-4 and obtained 12mer peptide mimics EPA. The experimental results show that EPA and Exendin4 can promote the proliferative activity of islet β cells, and the activity of EPA is 5%—25% higher than that of Exendin4 in the range of 40—200 μmol/L. EPA inhibits the apoptosis of islet β cells by inhibiting bax gene and upregulating bcl2 gene expression, and inhibiting Caspase3 activity at 100 mmol/L high concentration of glucose toxicity, EPA is a highactivity shortpeptide mimics of Exendin-4, which can inhibit the mitochondrial apoptosis through bcl-2/bax…Casepase3 signaling pathway.

Key words: peptide library screening, mimic of Exendin4, bioactivity, glucose toxicity