Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses

Helen M. Cox*, Iain R. Tough, Anne-Marie Woolston, Lei Zhang, Amy D. Nguyen, Amanda Sainsbury, Herbert Herzog

*Corresponding author for this work

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Peptide YY (PYY) is released following food intake and regulates intestinal function and glucose homeostasis, but the mechanisms underpinning these processes are unclear. Enteroendocrine L cells contain PYY and express the acylethanolamine receptor, Gpr119. Here, we show that Gpr119 activation inhibited epithelial electrolyte secretion in human and mouse colon in a glucose-sensitive manner. Endogenous PYY selectively mediated these effects, since PYY(-/-) mice showed no Gpr119 response, but responses were observed in NPY(-/-) mice. Importantly, Gpr119 responses in wild-type (WT) mouse tissue and human colon were abolished by Y(1) receptor antagonism, but were not enhanced by dipeptidylpeptidase IV blockade, indicating that PYY processing to PYY(3-36) was not important. In addition, Gpr119 agonism reduced glycemic excursions after oral glucose delivery to WT mice but not PYY(-/-) mice. Taken together, these data demonstrate a previously unrecognized role of PYY in mediating intestinal Gpr119 activity and an associated function in controlling glucose tolerance.

Original languageEnglish
Pages (from-to)532-542
Number of pages11
JournalCell Metabolism
Volume11
Issue number6
DOIs
Publication statusPublished - 9 Jun 2010
Externally publishedYes

Keywords

  • GLUCAGON-LIKE PEPTIDE-1
  • PROGLUCAGON-DERIVED PEPTIDES
  • PROTEIN-COUPLED RECEPTOR
  • MOUSE COLON MUCOSA
  • NEUROPEPTIDE-Y
  • PANCREATIC-POLYPEPTIDE
  • GLYCEMIC CONTROL
  • CELLS
  • MEDIATE
  • OBESITY

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