Identification of a bioactive peptide from Glycine max that stimulates the release of cholecystokinin and glucagon‐like peptide‐1 from enteroendocrine cells (372.1)

The goal of this study was to identify soy peptides that stimulate the release of two key satiety hormones, cholecystokinin (CCK) and glucagon‐like peptide‐1 (GLP‐1) from mouse enteroendocrine cells. To facilitate identification, bioactive soy hydrolysate was solubilized in starting mobile phase, fractionated using reversed‐phase HPLC, and assayed for bioactivity. Peptide sequences contained in high specific activity fractions were identified using nano‐LC‐Electrospray Ionization (ESI) Mass Spectrometry. Four of these were prepared synthetically and assayed for bioactivity. All four stimulated CCK release in a dose‐dependent fashion. One peptide (TSLDFPALSWLRL) stimulated CCK release that was 5‐fold greater than baseline (45+/‐ 1.7 vs 9 +/‐1.1 pg), and had an EC 50 value of 43 μM. It also stimulated dose‐dependent GLP‐1 release that was 1.7‐fold greater than baseline (74 +/‐ 14 vs 43 +/‐0.3 pg), and had an EC 50 value of 186 μM. Truncation of the first 5 N‐terminal amino acids, or the last three C‐terminal amino acids resulted in peptides with CCK and GLP‐1 release activities that were significantly greater than native peptides (169 +/‐18% and 153 +/‐16%, respectively for CCK release and 293 and 180%, respectively for GLP‐1 release). In conclusion, we have identified at least one peptide in bioactive soy hydrolysate responsible for satiety hormone release from enteroendocrine cells.