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

Enteroendocrine cells are thought to directly sense nutrients via ?-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).; We measured mRNA expression of ?-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.; ?-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 ?-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.; 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.