Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis. / Yassin, Mohammad; Sadowska, Zuzanna; Tritsaris, Katerina; Kissow, Hannelouise; Hansen, Camilla H F; Forman, Julie L; Rogler, Gerhard; Troelsen, Jesper T; Pedersen, Anders E; Olsen, Jørgen.

In: Journal of Crohn's and Colitis, Vol. 12, No. 12, 2018, p. 1459–1474.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Yassin, M, Sadowska, Z, Tritsaris, K, Kissow, H, Hansen, CHF, Forman, JL, Rogler, G, Troelsen, JT, Pedersen, AE & Olsen, J 2018, 'Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis', Journal of Crohn's and Colitis, vol. 12, no. 12, pp. 1459–1474. https://doi.org/10.1093/ecco-jcc/jjy112

APA

Yassin, M., Sadowska, Z., Tritsaris, K., Kissow, H., Hansen, C. H. F., Forman, J. L., ... Olsen, J. (2018). Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis. Journal of Crohn's and Colitis, 12(12), 1459–1474. https://doi.org/10.1093/ecco-jcc/jjy112

Vancouver

Yassin M, Sadowska Z, Tritsaris K, Kissow H, Hansen CHF, Forman JL et al. Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis. Journal of Crohn's and Colitis. 2018;12(12):1459–1474. https://doi.org/10.1093/ecco-jcc/jjy112

Author

Yassin, Mohammad ; Sadowska, Zuzanna ; Tritsaris, Katerina ; Kissow, Hannelouise ; Hansen, Camilla H F ; Forman, Julie L ; Rogler, Gerhard ; Troelsen, Jesper T ; Pedersen, Anders E ; Olsen, Jørgen. / Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis. In: Journal of Crohn's and Colitis. 2018 ; Vol. 12, No. 12. pp. 1459–1474.

Bibtex

@article{6fc22bdb7ec545aaac66a21ceef6e961,
title = "Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis",
abstract = "Background and Aims: Epithelial expression of the insulin receptor in the colon has previously been reported to correlate with extent of colonic inflammation. However, the impact of insulin signalling in the intestinal mucosa is still unknown. Here, we investigated the effects of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer.Methods: The mice were generated by utilizing the intestinal- and epithelial-specific villin promoter and the Cre-Lox technology. All mice included in the cohorts were generated by crossing [vil-Cre-INSR+/-] × [INSRfl/fl] to obtain [vil-Cre-INSR-/-], and their floxed littermates [INSRfl/fl] served as the control group. For the intervention study, phosphate-buffered saline with or without insulin was instilled rectally in anaesthetized wild-type mice with chemically induced colitis.Results: We found higher endoscopic colitis scores together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we showed that topically administered insulin in inflamed colons of wild-type mice reduced inflammation-induced weight loss and improved remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores and reduced cyclooxygenase 2 mRNA expression, and developed significantly fewer and smaller tumours compared with the control group receiving phosphate-buffered saline only.Conclusions: Rectal insulin therapy could potentially be a novel treatment, targeting the epithelial layer to enhance mucosal healing in ulcerated areas. Our findings open up new possibilities for combination treatments to synergize with the existing anti-inflammatory therapies.",
author = "Mohammad Yassin and Zuzanna Sadowska and Katerina Tritsaris and Hannelouise Kissow and Hansen, {Camilla H F} and Forman, {Julie L} and Gerhard Rogler and Troelsen, {Jesper T} and Pedersen, {Anders E} and J{\o}rgen Olsen",
year = "2018",
doi = "10.1093/ecco-jcc/jjy112",
language = "English",
volume = "12",
pages = "1459–1474",
journal = "Journal of Crohn's and Colitis",
issn = "1873-9946",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis

AU - Yassin, Mohammad

AU - Sadowska, Zuzanna

AU - Tritsaris, Katerina

AU - Kissow, Hannelouise

AU - Hansen, Camilla H F

AU - Forman, Julie L

AU - Rogler, Gerhard

AU - Troelsen, Jesper T

AU - Pedersen, Anders E

AU - Olsen, Jørgen

PY - 2018

Y1 - 2018

N2 - Background and Aims: Epithelial expression of the insulin receptor in the colon has previously been reported to correlate with extent of colonic inflammation. However, the impact of insulin signalling in the intestinal mucosa is still unknown. Here, we investigated the effects of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer.Methods: The mice were generated by utilizing the intestinal- and epithelial-specific villin promoter and the Cre-Lox technology. All mice included in the cohorts were generated by crossing [vil-Cre-INSR+/-] × [INSRfl/fl] to obtain [vil-Cre-INSR-/-], and their floxed littermates [INSRfl/fl] served as the control group. For the intervention study, phosphate-buffered saline with or without insulin was instilled rectally in anaesthetized wild-type mice with chemically induced colitis.Results: We found higher endoscopic colitis scores together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we showed that topically administered insulin in inflamed colons of wild-type mice reduced inflammation-induced weight loss and improved remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores and reduced cyclooxygenase 2 mRNA expression, and developed significantly fewer and smaller tumours compared with the control group receiving phosphate-buffered saline only.Conclusions: Rectal insulin therapy could potentially be a novel treatment, targeting the epithelial layer to enhance mucosal healing in ulcerated areas. Our findings open up new possibilities for combination treatments to synergize with the existing anti-inflammatory therapies.

AB - Background and Aims: Epithelial expression of the insulin receptor in the colon has previously been reported to correlate with extent of colonic inflammation. However, the impact of insulin signalling in the intestinal mucosa is still unknown. Here, we investigated the effects of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer.Methods: The mice were generated by utilizing the intestinal- and epithelial-specific villin promoter and the Cre-Lox technology. All mice included in the cohorts were generated by crossing [vil-Cre-INSR+/-] × [INSRfl/fl] to obtain [vil-Cre-INSR-/-], and their floxed littermates [INSRfl/fl] served as the control group. For the intervention study, phosphate-buffered saline with or without insulin was instilled rectally in anaesthetized wild-type mice with chemically induced colitis.Results: We found higher endoscopic colitis scores together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we showed that topically administered insulin in inflamed colons of wild-type mice reduced inflammation-induced weight loss and improved remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores and reduced cyclooxygenase 2 mRNA expression, and developed significantly fewer and smaller tumours compared with the control group receiving phosphate-buffered saline only.Conclusions: Rectal insulin therapy could potentially be a novel treatment, targeting the epithelial layer to enhance mucosal healing in ulcerated areas. Our findings open up new possibilities for combination treatments to synergize with the existing anti-inflammatory therapies.

U2 - 10.1093/ecco-jcc/jjy112

DO - 10.1093/ecco-jcc/jjy112

M3 - Journal article

VL - 12

SP - 1459

EP - 1474

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - 12

ER -

ID: 202030358