Activation of intestinal olfactory receptor stimulates glucagon-like peptide-1 secretion in enteroendocrine cells and attenuates hyperglycemia in type 2 diabetic mice

Scientific Reports
Ki-Suk KimHyeung-Jin Jang

Abstract

Odorants are non-nutrients. However, they exist abundantly in foods, wines, and teas, and thus can be ingested along with the other nutrients during a meal. Here, we have focused on the chemical-recognition ability of these ORs and hypothesized that the odorants ingested during a meal may play a physiological role by activating the gut-expressed ORs. Using a human-derived enteroendocrine L cell line, we discovered the geraniol- and citronellal-mediated stimulation of glucagon-like peptide-1 (GLP-1) secretion and elucidated the corresponding cellular downstream signaling pathways. The geraniol-stimulated GLP-1 secretion event in the enteroendocrine cell line was mediated by the olfactory-type G protein, the activation of adenylyl cyclase, increased intracellular cAMP levels, and extracellular calcium influx. TaqMan qPCR demonstrated that two ORs corresponding to geraniol and citronellal were expressed in the human enteroendocrine cell line and in mouse intestinal specimen. In a type 2 diabetes mellitus mouse model (db/db), oral administration of geraniol improved glucose homeostasis by increasing plasma GLP-1 and insulin levels. This insulinotropic action of geraniol was GLP-1 receptor-mediated, and also was glucose-dependent. T...Continue Reading

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Citations

Dec 7, 2018·Nature Reviews. Drug Discovery·Sung-Joon LeeHanns Hatt
Feb 29, 2020·International Journal of Molecular Sciences·Sachiko Koyama, Thomas Heinbockel
Apr 6, 2018·Genomics & Informatics·S June Oh
Jan 21, 2021·Frontiers in Cell and Developmental Biology·Elisabeth UrbauerDirk Haller
Feb 20, 2021·Critical Reviews in Food Science and Nutrition·Rifat Nowshin RakaJianming Jin
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jocelijn Meijerink
Apr 16, 2021·Bio-protocol·Snehal N Chaudhari, A Sloan Devlin
Aug 14, 2021·Critical Reviews in Food Science and Nutrition·José Fernando Rinaldi de AlvarengaJarlei Fiamoncini
Aug 20, 2021·British Journal of Pharmacology·Siyu ZhangHanbing Li
Nov 19, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ryan KurtzBlythe D Shepard
Mar 17, 2021··Snehal Chaudhari, Abigail Devlin

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Methods Mentioned

BETA
transfection
transfections
ELISA
PCR

Software Mentioned

InCyt Im2
Bio
GraphPad Prism
Primer express
Plex Manager

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