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

Clin Nutr. 2011 Aug;30(4):524-32. doi: 10.1016/j.clnu.2011.01.007. Epub 2011 Feb 15.

Abstract

Background & aims: Enteroendocrine cells are thought to directly sense nutrients via α-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 α-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: α-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 α-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzene Derivatives / administration & dosage
  • Colon / drug effects*
  • Enteroendocrine Cells / metabolism
  • Female
  • Glucagon-Like Peptide 1 / genetics
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucose / metabolism*
  • Humans
  • Ileum / drug effects*
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Peptide YY / genetics
  • Peptide YY / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Taste
  • Transducin / antagonists & inhibitors
  • Transducin / genetics
  • Transducin / metabolism

Substances

  • Benzene Derivatives
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • taste receptors, type 1
  • Peptide YY
  • Glucagon-Like Peptide 1
  • Transducin
  • Glucose
  • lactisole