Glucagon-like peptide-1 as a treatment for chemotherapy-induced mucositis

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 96h 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 48h, 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 48h after chemotherapy. The effect was equivalent. Exendin (9-39) reduced the intestinal weight 96h 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.