The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY)

Background Ea aims: Enteroendocrine cells are thought to directly sense nutrients via alpha-gustducin coupled taste receptors (originally identified in the oral epithelium) to modulate the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Methods: We measured mRNA expression of alpha-gustducin and T1R3 along the human gut; immunohistochemistry was used to confirm co-localization with GLP-1. Functional implication of sweet taste receptors in glucose-stimulated secretion of GLP-1 and PYY was determined by intragastric infusion of glucose with or without lactisole (a sweet taste receptor antagonist) in 16 healthy subjects. Results: alpha-gustducin was expressed in a region-specific manner (predominantly in the proximal gut and less in ileum and colon, P < 0.05). Both, T1R3 and alpha-gustducin were co-localized with GLP-1. Glucose-stimulated secretions of GLP-1 (P=0.026) and PYY (P=0.034) were reduced by blocking sweet receptors with lactisole. Conclusion: Key proteins implicated in taste signaling are present in the human gut and co-localized with GLP-1 suggesting that these proteins are functionally linked to peptide secretion from enteroendocrine cells. Glucose-stimulated secretion of GLP-1 and PYY is reduced by a sweet taste antagonist, suggesting the functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of both peptides in humans. (C) 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.