Glucagon-like peptide 2 induces vasoactive intestinal polypeptide expression in enteric neurons via phophatidylinositol 3-kinase-γ signaling

Heuvel, Elaine de; Wallace, Laurie E.; Sharkey, Keith A.; Sigalet, David L.

doi:10.1152/ajpendo.00291.2012

Cited by 54 publications

(47 citation statements)

References 44 publications

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“…This hormone is secreted by entero-endocrine L cells and acts indirectly through multiple downstream mediators (66). Its receptor (GLP-2R) is localized on distinct subpopulations of gut endocrine cells in the stomach, small intestine, and colon but also on subepithelial myofibroblasts (67,68). Hu et al showed a beneficial effect of intravenous GLP-2 injection in broilers on growth performance, intestinal morphology, villus height, and crypt cell proliferation (69).…”

Section: Discussionmentioning

confidence: 99%

Effects of Xylo-Oligosaccharides on Broiler Chicken Performance and Microbiota

Maesschalck

Eeckhaut

Maertens³

et al. 2015

Appl Environ Microbiol

195

153

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hIn broiler chickens, feed additives, including prebiotics, are widely used to improve gut health and to stimulate performance. Xylo-oligosaccharides (XOS) are hydrolytic degradation products of arabinoxylans that can be fermented by the gut microbiota. In the current study, we aimed to analyze the prebiotic properties of XOS when added to the broiler diet. Administration of XOS to chickens, in addition to a wheat-rye-based diet, significantly improved the feed conversion ratio. XOS significantly increased villus length in the ileum. It also significantly increased numbers of lactobacilli in the colon and Clostridium cluster XIVa in the ceca. Moreover, the number of gene copies encoding the key bacterial enzyme for butyrate production, butyryl-coenzyme A (butyryl-CoA):acetate CoA transferase, was significantly increased in the ceca of chickens administered XOS. In this group of chickens, at the species level, Lactobacillus crispatus and Anaerostipes butyraticus were significantly increased in abundance in the colon and cecum, respectively. In vitro fermentation of XOS revealed cross-feeding between L. crispatus and A. butyraticus. Lactate, produced by L. crispatus during XOS fermentation, was utilized by the butyrate-producing Anaerostipes species. These data show the beneficial effects of XOS on broiler performance when added to the feed, which potentially can be explained by stimulation of butyrate-producing bacteria through cross-feeding of lactate and subsequent effects of butyrate on gastrointestinal function. Cereal fibers are composed of carbohydrate polymers that are resistant to digestion in the small intestines of monogastric animals but are completely or partially fermented in the distal gut, and they are believed to stimulate gut health (1). The main components of the cereal fiber fraction are arabinoxylans (AX), pectins, resistant starch, cellulose, ␤-glucans, and lignin (2). Hydrolytic degradation of the heteropolymer AX results in a mixture of arabinose-substituted xylo-oligosaccharides (arabinoxylan-oligosaccharides) (AXOS) and nonsubstituted xylo-oligosaccharides (XOS) (3). XOS are oligomers consisting of xylose units linked through ␤-(1-4) linkages (4). Selective fermentation of XOS has been shown to induce changes in both the composition and activity of the gastrointestinal microbiota, improving the health and well-being of the host. This suggests that XOS could fulfill the definition of a prebiotic (5). The production of lactate and shortchain fatty acids (SCFA), including butyrate, upon fermentation of XOS, has been confirmed in several in vitro and in vivo studies (3, 6). Lactate can stimulate butyrate production due to crossfeeding between lactate-producing bacteria and lactate-utilizing butyrate-producing bacteria from Clostridium cluster XIVa (7). Butyrate has proven beneficial effects on gastrointestinal function, since it has anti-inflammatory properties, fuels epithelial cells, and increases the intestinal epithelial integrity. In addition, butyrate has been shown to improve growth pe...

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Section: Discussionmentioning

confidence: 99%

Effects of Xylo-Oligosaccharides on Broiler Chicken Performance and Microbiota

Maesschalck

Eeckhaut

Maertens³

et al. 2015

Appl Environ Microbiol

195

153

View full text Add to dashboard Cite

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“…GLP-2 signaling through subepithelial myofibroblasts induced the release of several growth factors (insulin-like growth factor-1, keratinocyte growth factor) responsible for the proliferative effects of GLP-2 (12,13,15,16,25,26,33,35,41). On the other hand, enteric neurons stimulation with GLP-2 induced the release of nitric oxide and vasoactive peptide mediating the anti-inflammatory and cytoprotective effects of GLP-2 (7,15,16,40,41). Concerning the enteroendocrine system, immunostaining studies have well documented the presence of GLP-2R in neuroendocrine cells in human and porcine intestine (15).…”

Section: Discussionmentioning

confidence: 99%

Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration

El-Jamal

Erdual

Neunlist

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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The glucagon-like peptide 2 (GLP-2) is an intestinotrophic hormone with growth promoting and anti-inflammatory actions. However, the full biological functions of GLP-2 and the localization of its receptor (GLP-2R) remain controversial. Among cell lines tested, the expression of GLP-2R transcript was detected in human colonic myofibroblasts (CCD-18Co) and in primary culture of rat enteric nervous system but not in intestinal epithelial cell lines, lymphocytes, monocytes, or endothelial cells. Surprisingly, GLP-2R was expressed in murine (GLUTag), but not human (NCI-H716) enteroendocrine cells. The screening of GLP-2R mRNA in mice organs revealed an increasing gradient of GLP-2R toward the distal gut. An unexpected expression was detected in the mesenteric fat, mesenteric lymph nodes, bladder, spleen, and liver, particularly in hepatocytes. In two mice models of trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis, the colonic expression of GLP-2R mRNA was decreased by 60% compared with control mice. Also, GLP-2R mRNA was significantly downregulated in intestinal tissues of inflammatory bowel disease patients. Therapeutically, GLP-2 showed a weak restorative effect on intestinal inflammation during TNBS-induced colitis as assessed by macroscopic score and inflammatory markers. Finally, GLP-2 treatment accelerated mouse liver regeneration following partial hepatectomy as assessed by histological and molecular analyses. In conclusion, the limited therapeutic effect of GLP-2 on colonic inflammation dampens its utility in the management of severe inflammatory intestinal disorders. However, the role of GLP-2 in liver regeneration is a novelty that might introduce GLP-2 into the management of liver diseases and emphasizes on the importance of elucidating other extraintestinal functions of GLP-2.

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“…Subsets of enteric neurons are also thought to express CCK1 and GLP2 receptors (142,143) and have additionally been found to contain Rxfp4, potentially mediating responses to the orexigenic gut hormone INSL5 (20). Whether these receptors are located in the same or in different individual neurons remains to be established.…”

Section: Sensing By the Ensmentioning

confidence: 99%