Abstract: Objective To screen and validate islet function related pancreatic endogenous peptides differentially expressed between adult and aging mice, and to explore its mechanism. Methods Candidate peptides that might be related to islet function were screened from pancreatic peptides differentially expressed in adult and aging mice by using bioinformatics technology. The liquid chromatography-tandem mass spectrometry-multiple reaction monitoring technology was used to quantitatively verify the expression difference of the candidate peptides between adult mice and aging mice. The effects of target peptides on the gene and protein expression of insulin transcription factors including pancreatic duodenal homeobox factor 1(Pdx1), tendon membrane fibrosarcoma gene homolog A (MafA) and NK6 transcription factor related 1 (NKX6.1) were evaluated though real-time quantitative polymerase chain reaction (RT-PCR) and western blot analysis. The effects of target peptides on insulin secretion level were examined by conducting a glucose-stimulated insulin secretion experiment. Results The content of seven candidate peptides down-regulated in aging mice was screened and verified. Finally, it was found that after treating MIN6 cells with 10 μmol/L KDKKGKGGTKT peptide for 3 hours, the gene and protein levels of Pdx1, MafA and NKX6.1 were increased and insulin secretion level in cells was increased under the stimulation of high gulcose (20 mmol/L), with all differences being significant (P<0.05 or P<0.01). Conclusions The differentially expressed peptides in the pancreas of adult and aging mice may participate in the biological process related to diabetes and islet function. The KDKKGKGGTKT peptide may improve the function of islet β-cell.

Key words: aging mouse, peptide, islet function, adult mouse