Glucagonlike peptide-2 analogue: a possible new approach in the management of inflammatory bowel disease

J Pediatr Surg. 2004 Mar;39(3):448-52; discussion 448-52. doi: 10.1016/j.jpedsurg.2003.11.024.

Abstract

Background/purpose: Glucagonlike peptide-2alpha (GLP-2alpha) has been shown to be a growth factor for the small intestine. This study investigated the benefits of intravenous and intraluminal administration of GLP-2alpha using a rat model of inflammatory bowel disease (IBD).

Methods: Normal Fisher rats and HLA-B27 (IBD) rats were treated for 14 days as follows: Fisher, intravenous saline (n = 6); HLA-B27, intravenous saline (n = 6); HLA-B27, intravenous GLP-2alpha (50 microg/kg/d; n = 5); Fisher, intraluminal saline (n = 5); HLA-B27, intraluminal saline (n = 5); or intraluminal GLP-2alpha (50 microg/kg/d; n = 5). Rats were evaluated for frequency of diarrhea, and the bowel was analyzed for gross and microscopic lesions. Statistical evaluations were determined using analysis of variance (ANOVA). A P value of.05 was significant.

Results: Intravenous GLP-2alpha decreased diarrhea and the number of bowel lesions (P <.05). Microscopic inflammation was reduced by 24% but was not statistically significant. Intraluminal GLP-2alpha decreased the number of small intestine lesions (P <.05) and the microscopic inflammation (P <.05) but did not significantly reduce diarrhea or the overall number of bowel lesions.

Conclusions: GLP-2alpha ameliorates the signs of IBD in HLA-B27 rats. Intravenous GLP-2alpha reduces diarrhea more effectively than intraluminal administration, and both routes are equally effective in ameliorating inflammation. GLP-2alpha potentially provides a new modality for the treatment of IBD.

MeSH terms

  • Analysis of Variance
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Defecation
  • Diarrhea / prevention & control
  • Disease Models, Animal
  • Female
  • Glucagon-Like Peptides
  • HLA-B27 Antigen
  • Ileum
  • Inflammatory Bowel Diseases / drug therapy*
  • Injections, Intravenous
  • Intestinal Mucosa / pathology
  • Peptides / administration & dosage*
  • Rats
  • Rats, Inbred F344
  • Rats, Mutant Strains

Substances

  • Anti-Inflammatory Agents
  • HLA-B27 Antigen
  • Peptides
  • Glucagon-Like Peptides
  • glucagon-like-immunoreactivity