8 research outputs found
Modulation of food intake by differential TAS2R stimulation in rat
Metabolic surgery modulates the enterohormone profile, which leads, among other effects, to changes in food intake. Bitter taste receptors (TAS2Rs) have been identified in the gastrointestinal tract and specific stimulation of these has been linked to the control of ghrelin secretion. We hypothesize that optimal stimulation of TAS2Rs could help to modulate enteroendocrine secretions and thus regulate food intake. To determine this, we have assayed the response to specific agonists for hTAS2R5, hTAS2R14 and hTAS2R39 on enteroendocrine secretions from intestinal segments and food intake in rats. We found that hTAS2R5 agonists stimulate glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK), and reduce food intake. hTAS2R14 agonists induce GLP1, while hTASR39 agonists tend to increase peptide YY (PYY) but fail to reduce food intake. The effect of simultaneously activating several receptors is heterogeneous depending on the relative affinity of the agonists for each receptor. Although detailed mechanisms are not clear, bitter compounds can stimulate differentially enteroendocrine secretions that modulate food intake in rats
Effects of Flavanols on Enteroendocrine Secretion
Some beneficial effects of grape seed proanthocyanidin extract (GSPE) can be explained by the modulation of enterohormone secretion. As GSPE comprises a combination of different molecules, the pure compounds that cause these effects need to be elucidated. The enterohormones and chemoreceptors present in the gastrointestinal tract differ between species, so if humans are to gain beneficial effects, species closer to humans—and humans themselves—must be used. We demonstrate that 100 mg/L of GSPE stimulates peptide YY (PYY) release, but not glucagon-like peptide 1 (GLP-1) release in the human colon. We used a pig ex vivo system that differentiates between apical and basolateral intestinal sides to analyse how apical stimulation with GSPE and its pure compounds affects the gastrointestinal tract. In pigs, apical GSPE treatment stimulates the basolateral release of PYY in the duodenum and colon and that of GLP-1 in the ascending, but not the descending colon. In the duodenum, luminal stimulation with procyanidin dimer B2 increased PYY secretion, but not CCK secretion, while catechin monomers (catechin/epicatechin) significantly increased CCK release, but not PYY release. The differential effects of GSPE and its pure compounds on enterohormone release at the same intestinal segment suggest that they act through chemosensors located apically and unevenly distributed along the gastrointestinal tract
Modulation of Food Intake by Differential TAS2R Stimulation in Rat
Metabolic surgery modulates the enterohormone profile, which leads, among other effects, to changes in food intake. Bitter taste receptors (TAS2Rs) have been identified in the gastrointestinal tract and specific stimulation of these has been linked to the control of ghrelin secretion. We hypothesize that optimal stimulation of TAS2Rs could help to modulate enteroendocrine secretions and thus regulate food intake. To determine this, we have assayed the response to specific agonists for hTAS2R5, hTAS2R14 and hTAS2R39 on enteroendocrine secretions from intestinal segments and food intake in rats. We found that hTAS2R5 agonists stimulate glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK), and reduce food intake. hTAS2R14 agonists induce GLP1, while hTASR39 agonists tend to increase peptide YY (PYY) but fail to reduce food intake. The effect of simultaneously activating several receptors is heterogeneous depending on the relative affinity of the agonists for each receptor. Although detailed mechanisms are not clear, bitter compounds can stimulate differentially enteroendocrine secretions that modulate food intake in rats
Regulation of enteroendocrine function by bioactive components through their interaction with bitter taste receptors
El sistema enteroendocrí es troba al tracte gastrointestinal i controla la gana i l’activitat pancreàtica endocrina, entre
altres funcions. Els compostos bioactius que estimulen aquest sistema són candidats terapèutics per tractar patologies
relacionades amb aquestes funcions. Prèviament s’ha identificat que un extracte de proantocianidines de llavors de
raïm (GSPE) és antidiabètic per les seves capacitats de millora de la funció de les cèl·lules i la seva capacitat
saciant, com a conseqüència en part de l’activació del sistema enteroendocrí. El nostre grup ha relacionat les
secrecions enteroendocrines induïdes per polifenols amb l'estimulació de receptors del gust amarg (TAS2R) in vitro,
però si això es reflecteix en una ingesta alterada encara és deconegut. Per això, és necessari comprendre millor
aquest sistema per poder desenvolupar millors estratègies terapèutiques.
Aquesta tesi aborda si les secrecions d’intererohormones induïdes per GSPE modulen la producció de glucagó
pancreàtic i si aquestes secrecions es regulen mitjançant l’estimulació específica de TAS2R que condueix a un control
diferencial de la ingesta d’aliments. Aquesta hipòtesi s’ha avaluat amb estudis in vivo en rates i estudis ex vivo en
mostres intestinals.
Hem identificat que el glucagó és més sensible que la insulina a GSPE, fet que es correlaciona amb una secreció
il·leal de GLP1 millorada.El sistema enteroendocrino se encuentra en el tracto gastrointestinal y controla el apetito y la actividad pancreática
endocrina, entre otras funciones. Los compuestos bioactivos que estimulan este sistema son candidatos terapéuticos
para tratar patologías relacionadas con estas funciones. Previamente se identificó que un extracto de
proantocianidinas de semillas de uva (GSPE) es antidiabético por sus capacidades de mejora de la función de las
células y su capacidad saciante, como consecuencia en parte activar del sistema enteroendocrino. Nuestro grupo
relacionó las secreciones enteroendocrinas inducidas por polifenoles con la estimulación de receptores del gusto
amargo (TAS2R) in vitro, pero si esto se refleja en una ingesta alterada aún se desconoce. Por esto, es necesario
comprender mejor este sistema para poder desarrollar mejores estrategias terapéuticas.
Esta tesis aborda si las secreciones enteroendocrinas inducidas por GSPE modulan la producción de glucagón
pancreático y si estas se regulan mediante la estimulación específica de TAS2R que conduce a un control diferencial
de la ingesta. Esta hipótesis se ha evaluado con estudios in vivo en ratas y estudios ex vivo en muestras intestinales.
Hemos identificado que el glucagón es más sensible que la insulina a GSPE, lo que se correlaciona con una secreción
ileal de GLP1 mejorada.The enteroendocrine system is located in the gastrointestinal tract and controls appetite and endocrine pancreatic
activity, among other functions. Thus, bioactive compounds that stimulate the enteroendocrine system are therapeutic
candidates for treating pathologies related to these functions. Previous research has identified a grape-seed
proanthocyanidin extract (GSPE) as antidiabetic for its -cell function enhancement abilities and its appetitesuppressing
activity at least partly through activating the enteroendocrine system. Moreover, our group has linked the
polyphenol-induced enteroendocrine secretions to the stimulation of some bitter taste receptors (TAS2R) in vitro, but
whether it results in an altered food intake has not been studied yet. Since little is known of the mechanisms used by
polyphenols to stimulate secretory mechanisms of the enteroendocrine system, there is a need to fully comprehend this
system to specifically target it with a therapeutic strategy.
For this reason, this thesis addressed whether GSPE-induced enterohormone secretions modulate pancreatic
glucagon production, and whether these secretions are regulated through the specific stimulation of TAS2R leading to
a differential control of food intake. This hypothesis was assessed with in vivo studies in rats and ex vivo studies in
intestinal samples
Functional and genomic comparative study of the bitter taste receptor family TAS2R: Insight into the role of human TAS2R5
Bitterness is perceived in humans by 25 subtypes of bitter taste receptors (hTAS2R) that range from broadly tuned to more narrowly tuned receptors. hTAS2R5 is one of the most narrowly tuned bitter taste receptors in humans. In this study, we review the literature on this receptor and show there is no consensus about its role. We then compare the possible role of hTAS2R5 with that of the proteins of the TAS2R family in rat, mouse, and pig. A phylogenetic tree of all mammalian TAS2R domain-containing proteins showed that human hTAS2R5 has no ortholog in pig, mouse, or rat genomes. By comparing the agonists that are common to hTAS2R5 and other members of the family, we observed that hTAS2R39 is the receptor that shares most agonists with hTAS2R5. In mouse, some of these agonists activate mTas2r105 and mTas2r144, which are distant paralogs of hTAS2R5. mTas2r144 seems to be the receptor that is most similar to hTAS2R5 because they are both activated by the same agonists and have affinities in the same range of values. Then, we can conclude that hTAS2R5 has a unique functional specificity in humans as it is activated by selective agonists and that its closest functional homolog in mouse is the phylogenetically distant mTas2r144.This research was funded by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa”, grant number AGL2017-83477-R, C. Grau-Bové received a doctoral research grant from the Martí Franqués program of the Universitat Rovira i Virgili. M. Pinent and X. Terra are Serra Húnter fellows. We would like to express our thanks to Judith Pérez for her contribution to this work
GLP1 Exerts Paracrine Activity in the Intestinal Lumen of Human Colon
GLP1 produced in the upper part of the gut is released after food intake and acts by activating insulin secretion, but the role of GLP1 in the colon, where it is predominantly produced, remains unknown. Here we characterized the apical versus basolateral secretion of GLP1 and PYY and the paracrine mechanisms of action of these enterohormones in the human colon. We stimulated human colon tissue in different ex vivo models with meat peptone and we used immunofluorescence to study the presence of canonical and non-canonical receptors of GLP1. We found that PYY and GLP1 are secreted mainly at the gut lumen in unstimulated and stimulated conditions. We detected DPP4 activity and found that GLP1R and GCGR are widely expressed in the human colon epithelium. Unlike GLP1R, GCGR is not expressed in the lamina propria, but it is located in the crypts of Lieberkühn. We detected GLP1R expression in human colon cell culture models. We show that the apical secretion of PYY and GLP1 occurs in humans, and we provide evidence that GLP1 has a potential direct paracrine function through the expression of its receptors in the colon epithelium, opening new therapeutic perspectives in the use of enterohormones analogues in metabolic pathologies
GLP1 Exerts Paracrine Activity in the Intestinal Lumen of Human Colon
GLP1 produced in the upper part of the gut is released after food intake and acts by activating insulin secretion, but the role of GLP1 in the colon, where it is predominantly produced, remains unknown. Here we characterized the apical versus basolateral secretion of GLP1 and PYY and the paracrine mechanisms of action of these enterohormones in the human colon. We stimulated human colon tissue in different ex vivo models with meat peptone and we used immunofluorescence to study the presence of canonical and non-canonical receptors of GLP1. We found that PYY and GLP1 are secreted mainly at the gut lumen in unstimulated and stimulated conditions. We detected DPP4 activity and found that GLP1R and GCGR are widely expressed in the human colon epithelium. Unlike GLP1R, GCGR is not expressed in the lamina propria, but it is located in the crypts of Lieberkühn. We detected GLP1R expression in human colon cell culture models. We show that the apical secretion of PYY and GLP1 occurs in humans, and we provide evidence that GLP1 has a potential direct paracrine function through the expression of its receptors in the colon epithelium, opening new therapeutic perspectives in the use of enterohormones analogues in metabolic pathologies