{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T07:05:27Z","timestamp":1761807927567},"reference-count":27,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2015,3,31]],"date-time":"2015-03-31T00:00:00Z","timestamp":1427760000000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2015,3]]},"abstract":"Abstract<\/jats:title>Background and Aim<\/jats:title>Luminal nutrients stimulate enteroendocrine L<\/jats:styled-content> cells to release gut hormones, including intestinotrophic glucagon\u2010like peptide\u20102 (GLP<\/jats:styled-content>\u20102). Because L<\/jats:styled-content> cells express the bile acid receptor TGR<\/jats:styled-content>5 and dipeptidyl peptidase\u2010IV<\/jats:styled-content> (DPPIV<\/jats:styled-content>) rapidly degrades GLP<\/jats:styled-content>s, we hypothesized that luminal TGR<\/jats:styled-content>5 activation may attenuate intestinal injury via GLP<\/jats:styled-content>\u20102 release, which is enhanced by DPPIV<\/jats:styled-content> inhibition.<\/jats:p><\/jats:sec>Methods<\/jats:title>Intestinal injury was induced in mice by administration of dextran sulfate sodium (DSS<\/jats:styled-content>) in drinking water (free access to water containing 5% DSS<\/jats:styled-content> for 7 days). The selective TGR<\/jats:styled-content>5 agonist betulinic acid (BTA<\/jats:styled-content>) and the DPPIV<\/jats:styled-content> inhibitor sitagliptin phosphate monohydrate (STG<\/jats:styled-content>) were administered orally for 7 days. Male C<\/jats:styled-content>57BL<\/jats:styled-content>\/6 mice (6\u20137 weeks old) were divided into five groups: normal control group, disease control group, BTA<\/jats:styled-content> low group (drinking water containing 15\u2009mg\/L BTA<\/jats:styled-content>), BTA<\/jats:styled-content> high group (50\u2009mg\/L BTA<\/jats:styled-content>), and BTA<\/jats:styled-content> high\u2009+\u2009STG<\/jats:styled-content> (3\u2009mg\/kg, i.g.) group.<\/jats:p><\/jats:sec>Results<\/jats:title>The selective TGR<\/jats:styled-content>5 agonist BTA<\/jats:styled-content> dose\u2010dependently suppressed disease activity index and mRNA<\/jats:styled-content> expression of the pro\u2010inflammatory cytokines interleukin (IL<\/jats:styled-content>)\u20101\u03b2, IL<\/jats:styled-content>\u20106, and tumor necrosis factor\u2010\u03b1 in the colon. Nevertheless, STG<\/jats:styled-content> administration had little additive effect on BTA<\/jats:styled-content>\u2010induced protection. Fibroblast activation protein mRNA<\/jats:styled-content> expression, but not expression of other DPP<\/jats:styled-content> family members, was increased in the colon of DSS<\/jats:styled-content>\u2010treated mice with increased mucosal DPPIV<\/jats:styled-content>. Co\u2010administration of the selective GLP<\/jats:styled-content>\u20102 antagonist GLP<\/jats:styled-content>\u20102 (3\u201333) reversed the effect of BTA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The selective TGR<\/jats:styled-content>5 agonist BTA<\/jats:styled-content> ameliorated DSS<\/jats:styled-content>\u2010induced colitis in mice via the GLP<\/jats:styled-content>\u20102 pathway with no effect of DPPIV<\/jats:styled-content> inhibition, suggesting that other DPP<\/jats:styled-content> enzymatic activity is involved in GLP<\/jats:styled-content>\u20102 degradation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12740","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T19:50:10Z","timestamp":1428004210000},"page":"60-65","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The effects of a TGR<\/scp>5 agonist and a dipeptidyl peptidase IV<\/scp> 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