Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice

Research output: Contribution to journalJournal articleResearchpeer-review

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Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice. / Hytting-Andreasen, Rasmus; Balk-Møller, Emilie; Hartmann, Bolette; Pedersen, Jens; Windeløv, Johanne Agerlin; Holst, Jens Juul; Kissow, Hannelouise.

In: PLoS ONE, Vol. 13, No. 6, e0198046, 2018, p. 1-14.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Hytting-Andreasen, R, Balk-Møller, E, Hartmann, B, Pedersen, J, Windeløv, JA, Holst, JJ & Kissow, H 2018, 'Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice', PLoS ONE, vol. 13, no. 6, e0198046, pp. 1-14. https://doi.org/10.1371/journal.pone.0198046

APA

Hytting-Andreasen, R., Balk-Møller, E., Hartmann, B., Pedersen, J., Windeløv, J. A., Holst, J. J., & Kissow, H. (2018). Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice. PLoS ONE, 13(6), 1-14. [e0198046]. https://doi.org/10.1371/journal.pone.0198046

Vancouver

Hytting-Andreasen R, Balk-Møller E, Hartmann B, Pedersen J, Windeløv JA, Holst JJ et al. Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice. PLoS ONE. 2018;13(6):1-14. e0198046. https://doi.org/10.1371/journal.pone.0198046

Author

Hytting-Andreasen, Rasmus ; Balk-Møller, Emilie ; Hartmann, Bolette ; Pedersen, Jens ; Windeløv, Johanne Agerlin ; Holst, Jens Juul ; Kissow, Hannelouise. / Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice. In: PLoS ONE. 2018 ; Vol. 13, No. 6. pp. 1-14.

Bibtex

@article{e4f1b915c8f9415892f5f7b5a81df4dd,
title = "Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice",
abstract = "OBJECTIVE: Mucositis is a side effect of chemotherapy seen in the digestive tract, with symptoms including pain, diarrhoea, inflammation and ulcerations. Our aim was to investigate whether endogenous glucagon-like peptide -1 and -2 (GLP-1 and GLP-2) are implicated in intestinal healing after chemotherapy-induced mucositis.DESIGN: We used a transgenic mouse model Tg(GCG.DTR)(Tg) expressing the human diphtheria toxin receptor in the proglucagon-producing cells. Injections with diphtheria toxin ablated the GLP-1 and GLP-2 producing L-cells in Tg mice with no effect in wild-type (WT) mice. Mice were injected with 5-fluorouracil or saline and received vehicle, exendin-4, teduglutide (gly2-GLP-2), or exendin-4/teduglutide in combination. The endpoints were body weight change, small intestinal weight, morphology, histological scoring of mucositis and myeloperoxidase levels.RESULTS: Ablation of L-cells led to impaired GLP-2 secretion; increased loss of body weight; lower small intestinal weight; lower crypt depth, villus height and mucosal area; and increased the mucositis severity score in mice given 5-fluorouracil. WT mice showed compensatory hyperproliferation as a sign of regeneration in the recovery phase. Co-treatment with exendin-4 and teduglutide rescued the body weight of the Tg mice and led to a hyperproliferation in the small intestine, whereas single treatment was less effective.CONCLUSION: The ablation of L-cells leads to severe mucositis and insufficient intestinal healing, shown by severe body weight loss and lack of compensatory hyperproliferation in the recovery phase. Co-treatment with exendin-4 and teduglutide could prevent this. Because both peptides were needed, we can conclude that both GLP-1 and GLP-2 are essential for intestinal healing in mice.",
author = "Rasmus Hytting-Andreasen and Emilie Balk-M{\o}ller and Bolette Hartmann and Jens Pedersen and Windel{\o}v, {Johanne Agerlin} and Holst, {Jens Juul} and Hannelouise Kissow",
year = "2018",
doi = "10.1371/journal.pone.0198046",
language = "English",
volume = "13",
pages = "1--14",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

RIS

TY - JOUR

T1 - Endogenous glucagon-like peptide- 1 and 2 are essential for regeneration after acute intestinal injury in mice

AU - Hytting-Andreasen, Rasmus

AU - Balk-Møller, Emilie

AU - Hartmann, Bolette

AU - Pedersen, Jens

AU - Windeløv, Johanne Agerlin

AU - Holst, Jens Juul

AU - Kissow, Hannelouise

PY - 2018

Y1 - 2018

N2 - OBJECTIVE: Mucositis is a side effect of chemotherapy seen in the digestive tract, with symptoms including pain, diarrhoea, inflammation and ulcerations. Our aim was to investigate whether endogenous glucagon-like peptide -1 and -2 (GLP-1 and GLP-2) are implicated in intestinal healing after chemotherapy-induced mucositis.DESIGN: We used a transgenic mouse model Tg(GCG.DTR)(Tg) expressing the human diphtheria toxin receptor in the proglucagon-producing cells. Injections with diphtheria toxin ablated the GLP-1 and GLP-2 producing L-cells in Tg mice with no effect in wild-type (WT) mice. Mice were injected with 5-fluorouracil or saline and received vehicle, exendin-4, teduglutide (gly2-GLP-2), or exendin-4/teduglutide in combination. The endpoints were body weight change, small intestinal weight, morphology, histological scoring of mucositis and myeloperoxidase levels.RESULTS: Ablation of L-cells led to impaired GLP-2 secretion; increased loss of body weight; lower small intestinal weight; lower crypt depth, villus height and mucosal area; and increased the mucositis severity score in mice given 5-fluorouracil. WT mice showed compensatory hyperproliferation as a sign of regeneration in the recovery phase. Co-treatment with exendin-4 and teduglutide rescued the body weight of the Tg mice and led to a hyperproliferation in the small intestine, whereas single treatment was less effective.CONCLUSION: The ablation of L-cells leads to severe mucositis and insufficient intestinal healing, shown by severe body weight loss and lack of compensatory hyperproliferation in the recovery phase. Co-treatment with exendin-4 and teduglutide could prevent this. Because both peptides were needed, we can conclude that both GLP-1 and GLP-2 are essential for intestinal healing in mice.

AB - OBJECTIVE: Mucositis is a side effect of chemotherapy seen in the digestive tract, with symptoms including pain, diarrhoea, inflammation and ulcerations. Our aim was to investigate whether endogenous glucagon-like peptide -1 and -2 (GLP-1 and GLP-2) are implicated in intestinal healing after chemotherapy-induced mucositis.DESIGN: We used a transgenic mouse model Tg(GCG.DTR)(Tg) expressing the human diphtheria toxin receptor in the proglucagon-producing cells. Injections with diphtheria toxin ablated the GLP-1 and GLP-2 producing L-cells in Tg mice with no effect in wild-type (WT) mice. Mice were injected with 5-fluorouracil or saline and received vehicle, exendin-4, teduglutide (gly2-GLP-2), or exendin-4/teduglutide in combination. The endpoints were body weight change, small intestinal weight, morphology, histological scoring of mucositis and myeloperoxidase levels.RESULTS: Ablation of L-cells led to impaired GLP-2 secretion; increased loss of body weight; lower small intestinal weight; lower crypt depth, villus height and mucosal area; and increased the mucositis severity score in mice given 5-fluorouracil. WT mice showed compensatory hyperproliferation as a sign of regeneration in the recovery phase. Co-treatment with exendin-4 and teduglutide rescued the body weight of the Tg mice and led to a hyperproliferation in the small intestine, whereas single treatment was less effective.CONCLUSION: The ablation of L-cells leads to severe mucositis and insufficient intestinal healing, shown by severe body weight loss and lack of compensatory hyperproliferation in the recovery phase. Co-treatment with exendin-4 and teduglutide could prevent this. Because both peptides were needed, we can conclude that both GLP-1 and GLP-2 are essential for intestinal healing in mice.

U2 - 10.1371/journal.pone.0198046

DO - 10.1371/journal.pone.0198046

M3 - Journal article

C2 - 29864142

VL - 13

SP - 1

EP - 14

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 6

M1 - e0198046

ER -

ID: 197962015