In:
Journal of Gastroenterology and Hepatology, Wiley, Vol. 30, No. S1 ( 2015-03), p. 60-65
Abstract:
Luminal nutrients stimulate enteroendocrine L cells to release gut hormones, including intestinotrophic glucagon‐like peptide‐2 ( GLP ‐2). Because L cells express the bile acid receptor TGR 5 and dipeptidyl peptidase‐ IV ( DPPIV ) rapidly degrades GLP s, we hypothesized that luminal TGR 5 activation may attenuate intestinal injury via GLP ‐2 release, which is enhanced by DPPIV inhibition. Methods Intestinal injury was induced in mice by administration of dextran sulfate sodium ( DSS ) in drinking water (free access to water containing 5% DSS for 7 days). The selective TGR 5 agonist betulinic acid ( BTA ) and the DPPIV inhibitor sitagliptin phosphate monohydrate ( STG ) were administered orally for 7 days. Male C 57 BL /6 mice (6–7 weeks old) were divided into five groups: normal control group, disease control group, BTA low group (drinking water containing 15 mg/L BTA ), BTA high group (50 mg/L BTA ), and BTA high + STG (3 mg/kg, i.g.) group. Results The selective TGR 5 agonist BTA dose‐dependently suppressed disease activity index and mRNA expression of the pro‐inflammatory cytokines interleukin ( IL )‐1β, IL ‐6, and tumor necrosis factor‐α in the colon. Nevertheless, STG administration had little additive effect on BTA ‐induced protection. Fibroblast activation protein mRNA expression, but not expression of other DPP family members, was increased in the colon of DSS ‐treated mice with increased mucosal DPPIV . Co‐administration of the selective GLP ‐2 antagonist GLP ‐2 (3–33) reversed the effect of BTA . Conclusion The selective TGR 5 agonist BTA ameliorated DSS ‐induced colitis in mice via the GLP ‐2 pathway with no effect of DPPIV inhibition, suggesting that other DPP enzymatic activity is involved in GLP ‐2 degradation.
Type of Medium:
Online Resource
ISSN:
0815-9319
,
1440-1746
DOI:
10.1111/jgh.2015.30.issue-s1
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2006782-3
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