A Lysozyme-Derived Peptide Induces GLP-1 Secretion in Mouse Jejunal Organoids and Modulates Glycemia in Rats

Protein digestion products promote the release of incretins, such as GLP-1, which regulate glucose homeostasis. Our previous studies demonstrated that the egg white peptide fraction stimulates GLP-1 secretion in STC-1 cells. Here, the GLP-1 secretion induced by the lysozyme-derived peptide ¹²³WIRGCRL¹²⁹ and six alanine-substituted analogues was evaluated in mouse jejunal organoids, alongside egg white digest and the amino acid phenylalanine (Phe). Phe induced a faster GLP-1 response, but the peptide ¹²³WIRGCRL¹²⁹ elicited a similar GLP-1 response, although tested at a 20-fold lower concentration. The GLP-1 release in organoids elicited by the peptide was 57.8 ± 5 pM, while Phe reached 43.7 ± 1 pM at 60 min. In STC-1 cells, the peptide induced 667.7 ± 24.2 pM of GLP-1 compared to 416.6 ± 40.1 pM induced by Phe. Results obtained in STC-1 suggested the involvement of ERK- and AMPK-mediated pathways in the GLP-1 secretion induced by the peptide. Oral glucose tolerance tests in Wistar rats after oral administration of ¹²³WIRGCRL¹²⁹ showed a reduction in glucose levels, while no changes were observed in the group receiving the amino acid mixture at equimolar concentration. These findings suggest the potential therapeutic application of some food peptides against type 2 diabetes.