{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:39:32Z","timestamp":1791848372270,"version":"4.3.4"},"reference-count":55,"publisher":"American Physiological Society","issue":"5","funder":[{"name":"Lucta SA","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture (USDA)","doi-asserted-by":"publisher","award":["3092-51000-060-01"],"award-info":[{"award-number":["3092-51000-060-01"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["DK-094616"],"award-info":[{"award-number":["DK-094616"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"Chinese Scholarship Council","doi-asserted-by":"crossref","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:p> Enteroendocrine L cells and glucagon-like peptide 2 (GLP-2) secretion are activated in the intestinal adaptation process following bowel resection in patients with short bowel syndrome. We hypothesized that enteral activation of Takeda G protein-coupled receptor 5 (TGR5), expressed in enteroendocrine L cells, could augment endogenous GLP-2 secretion and the intestinal adaptation response. Our aim was to assess the efficacy of different TGR5 agonists to stimulate GLP-2 secretion and intestinal adaptation in a piglet short-bowel model. In study 1, parenterally fed neonatal pigs ( n = 6\/group) were gavaged with vehicle, olive extract (OE; 10 or 50 mg\/kg), or ursolic acid (UA; 10 mg\/kg), and plasma GLP-2 was measured for 6 h. In study 2, neonatal pigs ( n = 6\u20138\/group) were subjected to transection or 80% mid-small intestine resection and, after 2 days, assigned to treatments for 10 days as follows: 1) transection + vehicle (sham), 2) resection + vehicle (SBS), 3) resection + 30 mg UA (SBS + UA), and 4) resection + 180 mg\/kg OE (SBS + OE). We measured plasma GLP-2, intestinal histology, cell proliferation, and gene expression, as well as whole body citrulline-arginine kinetics and bile acid profiles. In study 1, GLP-2 secretion was increased by UA and tended to be increased by OE. In study 2, SBS alone, but not additional treatment with either TGR5 agonist, resulted in increased mucosal thickness and crypt cell proliferation in remnant jejunum and ileum sections. SBS increased biliary and ileal concentration of bile acids and expression of inflammatory and farnesoid X receptor target genes, but these measures were suppressed by UA treatment. In conclusion, UA is an effective oral GLP-2 secretagogue in parenterally fed pigs but is not capable of augmenting GLP-2 secretion or the intestinal adaptation response after massive small bowel resection. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Therapeutic activation of endogenous glucagon-like peptide 2 (GLP-2) secretion is a promising strategy to improve intestinal adaptation in patients with short bowel syndrome. This study in neonatal pigs showed that oral supplementation with a selective Takeda G protein-coupled receptor 5 (TGR5) agonist is an effective approach to increase GLP-2 secretion. The results warrant further study to establish a more potent oral TGR5 agonist that can effectively improve intestinal adaptation in pediatric patients with SBS. <\/jats:p>","DOI":"10.1152\/ajpgi.00360.2018","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T10:02:10Z","timestamp":1553767330000},"page":"G641-G652","source":"Crossref","is-referenced-by-count":19,"title":["Differential action of TGR5 agonists on GLP-2 secretion and promotion of intestinal adaptation in a piglet short bowel model"],"prefix":"10.1152","volume":"316","author":[{"given":"Sen","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Stoll","sequence":"additional","affiliation":[{"name":"US Department of Agriculture\/Agricultural Research Service Children\u2019s Nutrition Research Center, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Robinson","sequence":"additional","affiliation":[{"name":"US Department of Agriculture\/Agricultural Research Service Children\u2019s Nutrition Research Center, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose J.","family":"Pastor","sequence":"additional","affiliation":[{"name":"Lucta S.A., Montorn\u00e8s del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Marini","sequence":"additional","affiliation":[{"name":"US Department of Agriculture\/Agricultural Research Service Children\u2019s Nutrition Research Center, Houston, Texas"},{"name":"Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1105-6600","authenticated-orcid":false,"given":"Ignacio R.","family":"Ipharraguerre","sequence":"additional","affiliation":[{"name":"Lucta S.A., Montorn\u00e8s del Vall\u00e8s, Spain"},{"name":"Institute of Human Nutrition and Food Science, University of Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolette","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens J.","family":"Holst","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Cruz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Michael E. 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