Document Detail

Administration of a dipeptidyl peptidase IV inhibitor enhances the intestinal adaptation in a mouse model of short bowel syndrome.
MedLine Citation:
PMID:  21719060     Owner:  NLM     Status:  MEDLINE    
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.
Manabu Okawada; Jens J Holst; Daniel H Teitelbaum
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-30
Journal Detail:
Title:  Surgery     Volume:  150     ISSN:  1532-7361     ISO Abbreviation:  Surgery     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-01     Completed Date:  2011-09-20     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  217-23     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 Mosby, Inc. All rights reserved.
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MeSH Terms
Adaptation, Physiological / drug effects
Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
Disease Models, Animal
Glucagon-Like Peptide 2 / metabolism
Intestine, Small / drug effects,  metabolism*,  surgery
Mice, Inbred C57BL
Short Bowel Syndrome / drug therapy*,  etiology
Grant Support
48109-0245//PHS HHS; 5 P03 CA46592/CA/NCI NIH HHS; R01 AI044076/AI/NIAID NIH HHS; R01 AI044076-13/AI/NIAID NIH HHS
Reg. No./Substance:
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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