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 CO2 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 Pro3GIP, 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 Pro3GIP or Ex-3(9-39), whereas GLP-2(3-33) inhibited l-Glu/IMP-induced DBS. Vasoactive intestinal peptide (VIP)(6–28) intravenously or NG-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.
Footnotes
This work was supported by a research grant from Ajinomoto, Inc. (Tokyo, Japan) (to Y.A.); a Department of Veterans Affairs Merit Review Award (to J.D.K.); the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01-DK54221] (to J.D.K.); and the Animal Core of the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant P30-DK0413] (to J. E. Rozengurt).
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.111.184788.
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ABBREVIATIONS:
- DBS
- duodenal bicarbonate secretion
- Ex
- exendin
- GIP
- glucose-dependent insulinotropic peptide
- GIP-R
- GIP receptor
- GLP
- glucagon-like peptide
- GLP-1R
- GLP-1 receptor
- GLP-2R
- GLP-2 receptor
- l-NAME
- NG-nitro-l-arginine methyl ester
- NO
- nitric oxide
- NVP DPP 728
- 6-[[2-[[2-(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethyl]amino]ethyl]amino-3-pyridinecarbononitrile
- PV
- portal vein
- T1R
- taste receptor type 1
- VIP
- vasoactive intestinal peptide
- VIP-R
- VIP receptor
- BSA
- bovine serum albumin
- COX
- cyclooxygenase
- EIA
- enzyme immunoassay
- PG
- prostaglandin.
- Received June 6, 2011.
- Accepted August 15, 2011.
- U.S. Government work not protected by U.S. copyright
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