The intestine is considered the largest endocrine organ in the body due to the variety and the relevance of the hormones secreted at this level. Digestion products from nutrients promote the release of anorexigenic hormones and incretins, such as GLP-1, which is involved in glucose homeostasis regulation. Our previous studies showed that the peptide fraction from egg white digests exerts a potent GLP-1 secretagogue effect in the enteroendocrine cell line STC-1. The screening of different gastrointestinal-resistant peptides in STC-1 cells, showed the sequences from lysozyme (LZ), 109VAWRNRCKGTD119 and 123WIRGCRL129 to be potent GLP-1 and CCK inducers. To determine the key sequence, amino acid deletions and a peptide library based on 123WIRGCRL129 was created. Our results showed a decrease in hormone release for the shorter form 125RGCRL129, and the relevance of 124Ile and the two amino acids at the C-terminal end for cell activation. GLP-1 secretion induced by peptide 123WIRGCRL129 and six alanine-substituted analogs was also assessed in mice jejunal organoids, along with an egg white gastrointestinal digest, and the amino acid Phe, as positive control. GLP-1 response induced by Phe was faster than that exerted by the whole digest or the LZ-derived peptide, but the peptide elicited similar GLP-1 response although it was tested at a 20 times-lower concentration than Phe (peptide at 1 mM vs Phe at 20 mM). Moreover, the results in jejunal organoids confirmed the relevance of the amino acid 124Ile in the LZ-derived peptide, the action of peptidases on 123Trp, and the involvement of ERK- and AMPK-mediated pathways in cell activation and GLP-1 secretion. Oral glucose tolerance tests in Wistar rats after oral administration of 123WIRGCRL129 at 0.1 mM showed a significantly reduction of the blood glucose levels compared to the glucose overload group, while no changes were found in the group receiving the corresponding amino acid mixture at the same concentration. Although more studies are needed to elucidate the mechanism of action of these and other peptides released during digestion, our finding suggest the potential therapeutic application of egg white peptides against type II diabetes.

This work has received financial funding from projects PID2019-107663RB-100 and PDC2022-133489-100 (Spanish Ministry of Science and Innovation MICINN/AEI/10.13039/501100011033) and the latter counting with funding from European Union NextGenerationEU/PRTR. SMVM is the recipient of contract (PIE 202070E069) from CSIC. CIBEROBN (CB22/03/00068) is an initiative of the Instituto de Salud Carlos III, Spain.

Resumen del trabajo presentado a la 8th International Conference on Food Digestion, celebrada en Porto (Portugal) del 9 al 11 de abril de 2024.

Peer reviewed