The DPP-IV inhibitor ER-319711 has a proliferative effect on the colonic epithelium and a minimal effect in the amelioration of colitis.

Abstract

Dipeptidyl-peptidase IV (DPP-IV) inhibitors are expected to prolong the half-life of Glucagon-like peptide (GLP-2) as well as GLP-1, and may result in the promotion of epithelial cell proliferation and regeneration. The aim of this study was to investigate whether a DPP-IV inhibitor can promote epithelial proliferation and attenuate dextran sodium sulfate (DSS)-induced colitis. Nine-week-old female C57/B6 mice were given a single dose of ER-319711 to assess the changes in plasma GLP-2 concentrations. Ten mice were divided into two groups: a vehicle group and an ER-319711 group. ER-319711 was administered orally for 7 days. The mice were then given bromodeoxyuridine (BrdU) intraperitoneally 2 h before sacrifice on day 7. Twenty-six mice were divided into three groups: a vehicle group, a DSS-induced colitis group and a DSS-induced colitis treated with ER-319711 group. The mice were given DSS for 5 days and sacrificed on day 14. Plasma GLP-2 levels were elevated in response to ER-319711. The ER-319711 group had a significantly decreased body weight from days 1 to 3. The number of BrdU positive cells per crypt and the crypt height were increased in the ER-319711 group. The DSS + ER-319711 group had a decreased body weight transition. The disease activity index and colon length showed an amelioration of colitis in the DSS + ER-319711 group. DPP-IV inhibitors are thought to promote the proliferation of the intestinal epithelium. However, the amelioration of DSS-induced colitis was only partial.

• Authors: Hiromitsu Ban, Shigeki Bamba, Hirotsugu Imaeda, Osamu Inatomi, Ayako Kobori, Masaya Sasaki, Tomoyuki Tsujikawa, Akira Andoh, Yoshihide Fujiyama
• Journal: Oncology reports (Oncol Rep) Vol. 25 Issue 6 Pg. 1699-703 (Jun 2011) ISSN: 1791-2431 [Electronic] Greece
• PMID: 21431278 (Publication Type: Journal Article)

Chemical References

• 7-but-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one
• Enzyme Inhibitors
• Piperazines
• Purines
• Dipeptidyl Peptidase 4

Topics

• Animals
• Cell Proliferation (drug effects)
• Colitis (drug therapy)
• Colon (drug effects)
• Dipeptidyl Peptidase 4 (drug effects, metabolism)
• Enzyme Inhibitors (pharmacology)
• Female
• Intestinal Mucosa (drug effects)
• Mice
• Mice, Inbred C57BL
• Piperazines (pharmacology)
• Purines (pharmacology)