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

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.

Type Journal
ISBN 1932-7420 (Electronic) 1550-4131 (Linking)
Authors Cox, H. M.; Tough, I. R.; Woolston, A. M.; Zhang, L.; Nguyen, A. D.; Sainsbury, A.; Herzog, H.;
Garvan Authors Prof Herbert Herzog , Dr Lei Zhang
Publisher Name CELL METAB
Published Date 2010-01-01 00:00:00
Published Volume 11
Published Issue 6
Published Pages 532-42
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20519124
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?10674_10933/10 Cox Cell Metab.pdf