| Administration of a dipeptidyl peptidase IV inhibitor enhances the intestinal adaptation in a mouse model of short bowel syndrome. | |
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MedLine Citation:
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PMID: 21719060 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Glucagon-like peptide-2 induces small intestine mucosal epithelial cell proliferation and may have benefit for patients who suffer from short bowel syndrome. However, glucagon-like peptide-2 is inactivated rapidly in vivo by dipeptidyl peptidase IV. Therefore, we hypothesized that selectively inhibiting dipeptidyl peptidase IV would prolong the circulating life of glucagon-like peptide-2 and lead to increased intestinal adaptation after development of short bowel syndrome. METHODS: Eight-week old C57BL/6J mice underwent a 50% proximal small bowel resection and were treated with either sitagliptin, a dipeptidyl peptidase IV-inhibitor, starting 1 day before surgery versus placebo. The efficacy of dipeptidyl peptidase IV-inhibitor was assessed 3 days after resection, including intestinal morphology, epithelial cell apoptosis, and epithelial cell proliferation. Adaptive mechanisms were assessed with quantitative real-time polymerase chain reaction, and plasma bioactive glucagon-like peptide-2 was measured by radioimmunoassay. RESULTS: Body weight loss and peripheral blood glucose levels did not change compared with short bowel syndrome controls. Dipeptidyl peptidase IV-inhibitor treatment led to significant increases in villus height and crypt depth. Dipeptidyl peptidase IV-inhibitor treatment did not change EC apoptosis rates significantly, but it did increase crypt epithelial cell proliferation significantly versus placebo-short bowel syndrome controls. Dipeptidyl peptidase IV-inhibitor treatment markedly increased messenger RNA expression of β-catenin and c-myc in ileal mucosa. Plasma glucagon-like peptide-2 levels increased significantly (∼ 40.9%) in dipeptidyl peptidase IV-inhibitor short bowel syndrome mice. CONCLUSION: Dipeptidyl peptidase IV-inhibitor treatment increased short bowel syndrome adaptation and might potentially be useful for short bowel syndrome patients. |
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Authors:
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Manabu Okawada; Jens J Holst; Daniel H Teitelbaum |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-06-30 |
Journal Detail:
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Title: Surgery Volume: 150 ISSN: 1532-7361 ISO Abbreviation: Surgery Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-01 Completed Date: 2011-09-20 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0417347 Medline TA: Surgery Country: United States |
Other Details:
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Languages: eng Pagination: 217-23 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2011 Mosby, Inc. All rights reserved. |
Affiliation:
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Section of Pediatric Surgery, Department of Surgery, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI 48109-0245, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptation, Physiological
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drug effects Animals Dipeptidyl-Peptidase IV Inhibitors / administration & dosage* Disease Models, Animal Glucagon-Like Peptide 2 / metabolism Intestine, Small / drug effects, metabolism*, surgery Mice Mice, Inbred C57BL Short Bowel Syndrome / drug therapy*, etiology |
| Grant Support | |
ID/Acronym/Agency:
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48109-0245//PHS HHS; 5 P03 CA46592/CA/NCI NIH HHS; R01 AI044076-13/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dipeptidyl-Peptidase IV Inhibitors; 0/Glucagon-Like Peptide 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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