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Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors

Treatment with exogenous GLP-2 has been shown to accelerate the growth of intestinal adenomas and adenocarcinomas in experimental models of colonic neoplasia, however, the role of endogenous GLP-2 in tumor promotion is less well known. Mice with a global deletion of the glucagon receptor (Gcgr(-/-))...

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Autores principales: Hunt, Jenna Elizabeth, Yassin, Mohammad, Olsen, Jørgen, Hartmann, Bolette, Holst, Jens Juul, Kissow, Hannelouise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181411/
https://www.ncbi.nlm.nih.gov/pubmed/34108943
http://dx.doi.org/10.3389/fendo.2021.695145
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author Hunt, Jenna Elizabeth
Yassin, Mohammad
Olsen, Jørgen
Hartmann, Bolette
Holst, Jens Juul
Kissow, Hannelouise
author_facet Hunt, Jenna Elizabeth
Yassin, Mohammad
Olsen, Jørgen
Hartmann, Bolette
Holst, Jens Juul
Kissow, Hannelouise
author_sort Hunt, Jenna Elizabeth
collection PubMed
description Treatment with exogenous GLP-2 has been shown to accelerate the growth of intestinal adenomas and adenocarcinomas in experimental models of colonic neoplasia, however, the role of endogenous GLP-2 in tumor promotion is less well known. Mice with a global deletion of the glucagon receptor (Gcgr(-/-)) display an increase in circulating GLP-1 and GLP-2. Due to the intestinotrophic nature of GLP-2, we hypothesized that Gcgr(-/-) mice would be more susceptible to colonic dysplasia in a model of inflammation-induced colonic carcinogenesis. Female Gcgr(-/-) mice were first characterized for GLP-2 secretion and in a subsequent study they were given a single injection with the carcinogen azoxymethane (7.5 mg/kg) and treated with dextran sodium sulfate (DSS) (3%) for six days (n=19 and 9). A cohort of animals (n=4) received a colonoscopy 12 days following DSS treatment and all animals were sacrificed after six weeks. Disruption of glucagon receptor signaling led to increased GLP-2 secretion (p<0.0001) and an increased concentration of GLP-2 in the pancreas of Gcgr(-/-) mice, coinciding with an increase in small intestinal (p<0.0001) and colonic (p<0.05) weight. Increased villus height was recorded in the duodenum (p<0.001) and crypt depth was increased in the duodenum and jejunum (p<0.05 and p<0.05). Disruption of glucagon receptor signaling did not affect body weight during AOM/DSS treatment, neither did it affect the inflammatory score assessed during colonoscopy or the number of large and small adenomas present at the end of the study period. In conclusion, despite the increased endogenous GLP-2 secretion Gcgr(-/-) mice were not more susceptible to AOM/DSS-induced tumors.
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spelling pubmed-81814112021-06-08 Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors Hunt, Jenna Elizabeth Yassin, Mohammad Olsen, Jørgen Hartmann, Bolette Holst, Jens Juul Kissow, Hannelouise Front Endocrinol (Lausanne) Endocrinology Treatment with exogenous GLP-2 has been shown to accelerate the growth of intestinal adenomas and adenocarcinomas in experimental models of colonic neoplasia, however, the role of endogenous GLP-2 in tumor promotion is less well known. Mice with a global deletion of the glucagon receptor (Gcgr(-/-)) display an increase in circulating GLP-1 and GLP-2. Due to the intestinotrophic nature of GLP-2, we hypothesized that Gcgr(-/-) mice would be more susceptible to colonic dysplasia in a model of inflammation-induced colonic carcinogenesis. Female Gcgr(-/-) mice were first characterized for GLP-2 secretion and in a subsequent study they were given a single injection with the carcinogen azoxymethane (7.5 mg/kg) and treated with dextran sodium sulfate (DSS) (3%) for six days (n=19 and 9). A cohort of animals (n=4) received a colonoscopy 12 days following DSS treatment and all animals were sacrificed after six weeks. Disruption of glucagon receptor signaling led to increased GLP-2 secretion (p<0.0001) and an increased concentration of GLP-2 in the pancreas of Gcgr(-/-) mice, coinciding with an increase in small intestinal (p<0.0001) and colonic (p<0.05) weight. Increased villus height was recorded in the duodenum (p<0.001) and crypt depth was increased in the duodenum and jejunum (p<0.05 and p<0.05). Disruption of glucagon receptor signaling did not affect body weight during AOM/DSS treatment, neither did it affect the inflammatory score assessed during colonoscopy or the number of large and small adenomas present at the end of the study period. In conclusion, despite the increased endogenous GLP-2 secretion Gcgr(-/-) mice were not more susceptible to AOM/DSS-induced tumors. Frontiers Media S.A. 2021-05-24 /pmc/articles/PMC8181411/ /pubmed/34108943 http://dx.doi.org/10.3389/fendo.2021.695145 Text en Copyright © 2021 Hunt, Yassin, Olsen, Hartmann, Holst and Kissow https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Hunt, Jenna Elizabeth
Yassin, Mohammad
Olsen, Jørgen
Hartmann, Bolette
Holst, Jens Juul
Kissow, Hannelouise
Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors
title Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors
title_full Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors
title_fullStr Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors
title_full_unstemmed Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors
title_short Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors
title_sort intestinal growth in glucagon receptor knockout mice is not associated with the formation of aom/dss-induced tumors
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181411/
https://www.ncbi.nlm.nih.gov/pubmed/34108943
http://dx.doi.org/10.3389/fendo.2021.695145
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