Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses
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.
|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.;|
|Publisher Name||Cell Metabolism|
|Published Date||2010-01-01 00:00:00|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20519124|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10674|