title: Administration of a dipeptidyl peptidase IV inhibitor enhances the intestinal adaptation in a mouse model of short bowel syndrome.
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.
  
  
  CONCLUSIONS
  Dipeptidyl peptidase IV-inhibitor treatment increased short bowel syndrome adaptation and might potentially be useful for short bowel syndrome patients.
authors: Section of Pediatric Surgery, Department of Surgery, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI 48109-0245, USA.
authors: Manabu
authors: M
authors: Okawada
authors: Jens J
authors: JJ
authors: Holst
authors: Daniel H
authors: DH
authors: Teitelbaum
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D053767:Glucagon-Like Peptide 2 / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000209:etiology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D053767:Glucagon-Like Peptide 2