title: Glucagon-like peptide-1-(7-36) amide and peptide YY mediate intraduodenal fat-induced inhibition of acid secretion in dogs.
abstract: Intraduodenal fat inhibits gastric acid secretion via the release of one or more hormonal enterogastrones thought to arise from ileocolonic mucosa. This study determined whether glucagon-like peptide-1 (GLP-1)-(7-36) amide and peptide YY (PYY), colocalized in L cells found in the ileum, mediate intraduodenal fat-induced inhibition of stimulated gastric acid, and evaluated the influence of cholecystokinin-A (CCK-A) receptor activation. Gastric acid secretion in response to duodenal perfusions of 8% peptone was measured in conscious dogs with gastric and duodenal cannulas. Intraduodenal administration of a 10% fat emulsion suppressed gastric acid secretion by 72 +/- 4% (P < 0.001) and increased plasma levels of GLP-1 and PYY by 44 +/- 5 and 46 +/- 4 fmol/ml, respectively (both P < 0.01). Pretreatment with the CCK-A receptor antagonist MK-329 completely reversed the inhibition of gastric acid by fat, suppressed rises of plasma GLP-1 (maximum change, 23 +/- 4 fmol/ml), and reduced plasma PYY responses to baseline. Intravenous infusions of 50 pmol/kg x h GLP-1 or PYY, which reproduced plasma elevations after intraduodenal fat, inhibited gastric acid secretion by 66 +/- 5% and 51 +/- 6%, respectively (both P < 0.01); coinfusions of GLP-1 and PYY abolished gastric acid secretion (P < 0.001) without influencing plasma gastrin or somatostatin. Pretreatment with 1500 pmol/kg x h of the GLP-1 antagonist exendin-(9-39) amide did not alter the magnitude of inhibition of gastric acid caused by exogenous GLP-1. These results indicate that GLP-1 and PYY released by intraduodenal fat, in part through CCK-dependent pathways, are major enterogastrones in dogs. This inhibitory action occurs independent of circulating concentrations of somatostatin and gastrin and appears to involve a GLP-1 receptor distinct from that mediating incretin effects.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: L C
authors.initials: LC
authors.lastname: Fung
authors.forename: C
authors.initials: C
authors.lastname: Chisholm
authors.forename: G R
authors.initials: GR
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D020109:Devazepide; D004285:Dogs; D004386:Duodenum / Q000502:physiology*; D005223:Fats / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D019894:Peptide YY / Q000097:blood / Q000494:pharmacology*; D011498:Protein Precursors / Q000097:blood
chemical_list: D001570:Benzodiazepinones; D005223:Fats; D010446:Peptide Fragments; D011498:Protein Precursors; D019894:Peptide YY; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D020109:Devazepide