title: Umami receptor activation increases duodenal bicarbonate secretion via glucagon-like peptide-2 release in rats.
abstract: Luminal nutrient chemosensing during meal ingestion is mediated by intestinal endocrine cells, which regulate secretion and motility via the release of gut hormones. We have reported that luminal coperfusion of L-Glu and IMP, common condiments providing the umami or proteinaceous taste, synergistically increases duodenal bicarbonate secretion (DBS) possibly via taste receptor heterodimers, taste receptor type 1, member 1 (T1R1)/R3. We hypothesized that glucose-dependent insulinotropic peptide (GIP) or glucagon-like peptide (GLP) is released by duodenal perfusion with L-Glu/IMP. We measured DBS with pH and CO(2) electrodes through a perfused rat duodenal loop in vivo. GIP, exendin (Ex)-4 (GLP-1 receptor agonist), or GLP-2 was intravenously infused (0.01-1 nmol/kg/h). l-Glu (10 mM) and IMP (0.1 mM) were luminally perfused with or without bolus intravenous injection (3 or 30 nmol/kg) of the receptor antagonists Pro(3)GIP, Ex-3(9-39), or GLP-2(3-33). GIP or GLP-2 infusion dose-dependently increased DBS, whereas Ex-4 infusion gradually decreased DBS. Luminal perfusion of l-Glu/IMP increased DBS, with no effect of Pro(3)GIP or Ex-3(9-39), whereas GLP-2(3-33) inhibited L-Glu/IMP-induced DBS. Vasoactive intestinal peptide (VIP)(6-28) intravenously or N(G)-nitro-L-arginine methyl ester coperfusion inhibited the effect of L-Glu/IMP. Perfusion of L-Glu/IMP increased portal venous concentrations of GLP-2, followed by a delayed increase of GLP-1, with no effect on GIP release. GLP-1/2 and T1R1/R3 were expressed in duodenal endocrine-like cells. These results suggest that luminal L-Glu/IMP-induced DBS is mediated via GLP-2 release and receptor activation followed by VIP and nitric oxide release. Because GLP-1 is insulinotropic and GLP-2 is intestinotrophic, umami receptor activation may have additional benefits in glucose metabolism and duodenal mucosal protection and regeneration.
authors.affiliation: Department of Medicine, School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Joon-Ho
authors.initials: JH
authors.lastname: Wang
authors.forename: Takuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashiyama
authors.forename: Paul H
authors.initials: PH
authors.lastname: Guth
authors.forename: Eli
authors.initials: E
authors.lastname: Engel
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kaunitz
authors.forename: Yasutada
authors.initials: Y
authors.lastname: Akiba
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D000077270:Exenatide; D005749:Gastric Inhibitory Polypeptide / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D018698:Glutamic Acid / Q000008:administration & dosage / Q000378:metabolism; D007291:Inosine Monophosphate / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018027:Receptors, Glucagon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014688:Venoms / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; C000593835:Glp1r protein, rat; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D011976:Receptors, Muscarinic; D018005:Receptors, Vasoactive Intestinal Peptide; D014688:Venoms; C549100:pro-glucose-dependent insulinotropic polypeptide; C431926:taste receptors, type 1; C113198:vasoactive intestinal peptide (6-28); C049962:gastric inhibitory polypeptide (1-39); C066448:exendin 3; D007291:Inosine Monophosphate; D014660:Vasoactive Intestinal Peptide; D018698:Glutamic Acid; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; C041086:gastric inhibitory polypeptide receptor; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester