Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Aug;150(2):217-23.
doi: 10.1016/j.surg.2011.05.013. Epub 2011 Jun 30.

Administration of a Dipeptidyl Peptidase IV Inhibitor Enhances the Intestinal Adaptation in a Mouse Model of Short Bowel Syndrome

Affiliations
Free PMC article

Administration of a Dipeptidyl Peptidase IV Inhibitor Enhances the Intestinal Adaptation in a Mouse Model of Short Bowel Syndrome

Manabu Okawada et al. Surgery. .
Free PMC article

Abstract

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.

Figures

Figure 1
Figure 1
Time course of peripheral blood glucose levels in each study group. Peripheral blood for measuring glucose level was taken daily from the tail vein. Values are means ± SEM. N=5–6.
Figure 2
Figure 2
Representative immunofluorescent images of jejunum and ileum are shown (left panels) after undergoing BrdU/DAPI staining (20X magnification) 3 days after a 50% small bowel resection. Indices of crypt cell proliferation rates are shown in the graphs (right panels). Note that the proliferation index was significantly increased in SBS+DPPIV-I mice. Results are shown as the mean ± SEM. Statistical comparisons are made using ANOVA with post hoc Bonferroni test. N=5–6. Scale bars:50μm
Figure 3
Figure 3
Plasma concentration of bioactive glucagon-like peptide-2 (GLP-2) levels. Values are means ± SEM. N=5–6. *P<0.05

Similar articles

See all similar articles

Cited by 12 articles

See all "Cited by" articles

Publication types

MeSH terms

Substances

Feedback