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Gut. 2013 Dec;62(12):1724-33. doi: 10.1136/gutjnl-2012-303280. Epub 2012 Oct 20.

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

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1
Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.

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.

KEYWORDS:

Chemotherapy; Gastrointestinal Peptides; Gut Hormones; Mucosal Injury; Mucosal Repair

PMID:
23086829
DOI:
10.1136/gutjnl-2012-303280
[Indexed for MEDLINE]
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