title: Glucagon-like peptide-1 as a treatment for chemotherapy-induced mucositis.
abstract: BACKGROUND
  Glucagon-like peptide-2 (GLP-2) has been suggested for the treatment of mucositis, but the peptide has also been shown to accentuate colonic dysplasia in carcinogen-treated mice. Recently, an effect on intestinal growth was discovered for glucagon-like peptide-1 (GLP-1), OBJECTIVE: To determine whether endogenous GLP-1 contributes to the healing processes and if exogenous GLP-1 has a potential role in treating mucositis.
  
  
  METHODS
  Mice were injected with 5-fluorouracil (5-FU) or saline to induce mucositis and were then treated with GLP-1, GLP-2, GLP-2 (3-33), exendin (9-39) or vehicle. The mice were sacrificed 48 or 96 h after the 5-FU injections. The end points were intestinal weight, villus height, proliferation and histological scoring of mucositis severity. Rats were injected with 5-FU or saline, and after 48 h, blood was drawn and analysed for GLP-1 and GLP-2 concentration.
  
  
  RESULTS
  GLP-1 and GLP-2 significantly prevented the loss of mucosal mass and villus height and significantly decreased the mucositis severity score in the duodenum and jejunum 48 h after chemotherapy. The effect was equivalent. Exendin (9-39) reduced the intestinal weight 96 h after chemotherapy. The GLP-1 levels in blood were increased more than 10-fold, and GLP-2 levels were increased sevenfold.
  
  
  CONCLUSIONS
  GLP-1 and GLP-2 were secreted after intestinal injury, and recovery was delayed after treatment with exendin (9-39), indicating an important role for the peptides in the protection of the intestine from injury. GLP-1 treatment ameliorated mucositis, which suggests that mucositis and other acute intestinal disorders might benefit from treatment with GLP-1 analogues.
authors.affiliation: Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hannelouise
authors.initials: H
authors.lastname: Kissow
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Steen Seier
authors.initials: SS
authors.lastname: Poulsen
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D053767:Glucagon-Like Peptide 2 / Q000627:therapeutic use; D007410:Intestinal Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D051379:Mice; D052016:Mucositis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010446:Peptide Fragments / Q000627:therapeutic use; D017208:Rats, Wistar
chemical_list: D000964:Antimetabolites, Antineoplastic; D053767:Glucagon-Like Peptide 2; D010446:Peptide Fragments; C451520:glucagon-like peptide-2 (3-33); C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005472:Fluorouracil
keywords: Chemotherapy; Gastrointestinal Peptides; Gut Hormones; Mucosal Injury; Mucosal Repair