title: 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: Division of Gastroenterology, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga 520-2192, Japan.
authors: Hiromitsu
authors: H
authors: Ban
authors: Shigeki
authors: S
authors: Bamba
authors: Hirotsugu
authors: H
authors: Imaeda
authors: Osamu
authors: O
authors: Inatomi
authors: Ayako
authors: A
authors: Kobori
authors: Masaya
authors: M
authors: Sasaki
authors: Tomoyuki
authors: T
authors: Tsujikawa
authors: Akira
authors: A
authors: Andoh
authors: Yoshihide
authors: Y
authors: Fujiyama
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*
chemical_list: C515927:7-but-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one; D004791:Enzyme Inhibitors; D010879:Piperazines; D011687:Purines; D018819:Dipeptidyl Peptidase 4