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Gut. 2004 Aug;53(8):1145-50.

Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice.

Author information

1
Department of Medical Anatomy, Section B, The Panum Institute, University of Copenhagen, Copenhagen, Denmark. J.Thulesen@dadlnet.dk

Abstract

BACKGROUND:

Glucagon-like peptide 2 (GLP-2) is an intestinotrophic mediator with therapeutic potential in conditions with compromised intestinal capacity. However, growth stimulation of the intestinal system may accelerate the growth of existing neoplasms in the intestine.

AIMS:

In the present study, the effects of GLP-2 treatment on the growth of chemically induced colonic neoplasms were investigated.

METHODS:

In 210 female C57bl mice, colonic tumours were initially induced with the methylating carcinogen 1,2-dimethylhydrazine (DMH) and mice were then treated with GLP-2. Two months after discontinuation of the carcinogen treatment, 135 of the mice were allocated to one of six groups which were treated twice daily with 25 microg GLP-2, 25 microg Gly2-GLP-2 (stable analogue), or phosphate buffered saline for a short (10 days) or long (one month) period. The remaining 75 mice had a treatment free period of three months and were then allocated to groups subjected to long term treatment, as above.

RESULTS:

Colonic polyps developed in 100% of the mice, regardless of treatment. Survival data revealed no statistical significant differences among the different groups but histopathological analysis demonstrated a clear and significant increase in tumour load of mice treated with Gly2-GLP-2. The tumour promoting effect of native GLP-2 was less pronounced but the number of small sized polyps increased following long term treatment.

CONCLUSIONS:

The present results clearly indicate that GLP-2 promotes the growth of mucosal neoplasms. Our findings highlight the need for future investigations on the effects of GLP-2 in conditions needing long time treatment or with increased gastrointestinal cancer susceptibility.

PMID:
15247183
PMCID:
PMC1774162
DOI:
10.1136/gut.2003.035212
[Indexed for MEDLINE]
Free PMC Article

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