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 journalArticlepeer-review

75 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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