Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice
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Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice. / Thulesen, J; Hartmann, B; Hare, K J; Kissow, H; Ørskov, C; Holst, Jens Juul; Poulsen, S S.
In: Gut, Vol. 53, No. 8, 08.2004, p. 1145-1150.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice
AU - Thulesen, J
AU - Hartmann, B
AU - Hare, K J
AU - Kissow, H
AU - Ørskov, C
AU - Holst, Jens Juul
AU - Poulsen, S S
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
KW - Adenoma
KW - Animals
KW - Body Weight
KW - Colonic Neoplasms
KW - Colonic Polyps
KW - Female
KW - Glucagon-Like Peptide 2
KW - Glucagon-Like Peptides
KW - Intestinal Mucosa
KW - Intestine, Small
KW - Mice
KW - Mice, Inbred C57BL
KW - Organ Size
KW - Peptides
U2 - 10.1136/gut.2003.035212
DO - 10.1136/gut.2003.035212
M3 - Journal article
C2 - 15247183
VL - 53
SP - 1145
EP - 1150
JO - Gut
JF - Gut
SN - 0017-5749
IS - 8
ER -
ID: 132054279