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

M Yassin, Zusanna Sadowska, K Tritsaris, H Kissow, CHF Hansen, JL Forman, G Rogler, Jesper Troelsen, AE Pedersen, J Olsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background & AimsThe epithelial expression of the insulin receptor in the colon is previously reported to correlate with the extent of colonic inflammation. However, the impact of insulin signaling 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.
MethodsThe 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+/-) x (INSRfl/fl) to obtain (vil-Cre-INSR-/-) and their floxed littermates (INSRfl/fl) serving as the control group. For the intervention study, phosphate-buffered saline with or without insulin was instilled rectally in anesthetized wild type mice with chemically-induced colitis.
ResultsWe report higher endoscopic colitis scores together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we show that topically administered insulin in inflamed colons of wildtype mice reduces inflammation-induced weight loss and improves remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores, reduced cyclooxygenase 2 mRNA expression, and developed significantly fewer and smaller tumors compared with the control group receiving phosphate-buffered saline only.
OriginalsprogEngelsk
TidsskriftJournal of Crohn's and Colitis
Vol/bind12
Udgave nummer12
Sider (fra-til)1459–1474
ISSN1873-9946
DOI
StatusUdgivet - 2018

Citer dette

Yassin, M., Sadowska, Z., Tritsaris, K., Kissow, H., Hansen, CHF., Forman, JL., ... 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
Yassin, M ; Sadowska, Zusanna ; Tritsaris, K ; Kissow, H ; Hansen, CHF ; Forman, JL ; Rogler, G ; Troelsen, Jesper ; Pedersen, AE ; Olsen, J. / Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis. I: Journal of Crohn's and Colitis. 2018 ; Bind 12, Nr. 12. s. 1459–1474.
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title = "Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis",
abstract = "Background & AimsThe epithelial expression of the insulin receptor in the colon is previously reported to correlate with the extent of colonic inflammation. However, the impact of insulin signaling 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.MethodsThe 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+/-) x (INSRfl/fl) to obtain (vil-Cre-INSR-/-) and their floxed littermates (INSRfl/fl) serving as the control group. For the intervention study, phosphate-buffered saline with or without insulin was instilled rectally in anesthetized wild type mice with chemically-induced colitis.ResultsWe report higher endoscopic colitis scores together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we show that topically administered insulin in inflamed colons of wildtype mice reduces inflammation-induced weight loss and improves remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores, reduced cyclooxygenase 2 mRNA expression, and developed significantly fewer and smaller tumors compared with the control group receiving phosphate-buffered saline only.",
author = "M Yassin and Zusanna Sadowska and K Tritsaris and H Kissow and CHF Hansen and JL Forman and G Rogler and Jesper Troelsen and AE Pedersen and J Olsen",
year = "2018",
doi = "10.1093/ecco-jcc/jjy112",
language = "English",
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pages = "1459–1474",
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Yassin, M, Sadowska, Z, Tritsaris, K, Kissow, H, Hansen, CHF, Forman, JL, Rogler, G, Troelsen, J, Pedersen, AE & Olsen, J 2018, 'Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis', Journal of Crohn's and Colitis, bind 12, nr. 12, s. 1459–1474. https://doi.org/10.1093/ecco-jcc/jjy112

Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis. / Yassin, M; Sadowska, Zusanna; Tritsaris, K; Kissow, H; Hansen, CHF; Forman, JL; Rogler, G; Troelsen, Jesper; Pedersen, AE; Olsen, J.

I: Journal of Crohn's and Colitis, Bind 12, Nr. 12, 2018, s. 1459–1474.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

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

AU - Yassin, M

AU - Sadowska, Zusanna

AU - Tritsaris, K

AU - Kissow, H

AU - Hansen, CHF

AU - Forman, JL

AU - Rogler, G

AU - Troelsen, Jesper

AU - Pedersen, AE

AU - Olsen, J

PY - 2018

Y1 - 2018

N2 - Background & AimsThe epithelial expression of the insulin receptor in the colon is previously reported to correlate with the extent of colonic inflammation. However, the impact of insulin signaling 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.MethodsThe 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+/-) x (INSRfl/fl) to obtain (vil-Cre-INSR-/-) and their floxed littermates (INSRfl/fl) serving as the control group. For the intervention study, phosphate-buffered saline with or without insulin was instilled rectally in anesthetized wild type mice with chemically-induced colitis.ResultsWe report higher endoscopic colitis scores together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we show that topically administered insulin in inflamed colons of wildtype mice reduces inflammation-induced weight loss and improves remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores, reduced cyclooxygenase 2 mRNA expression, and developed significantly fewer and smaller tumors compared with the control group receiving phosphate-buffered saline only.

AB - Background & AimsThe epithelial expression of the insulin receptor in the colon is previously reported to correlate with the extent of colonic inflammation. However, the impact of insulin signaling 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.MethodsThe 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+/-) x (INSRfl/fl) to obtain (vil-Cre-INSR-/-) and their floxed littermates (INSRfl/fl) serving as the control group. For the intervention study, phosphate-buffered saline with or without insulin was instilled rectally in anesthetized wild type mice with chemically-induced colitis.ResultsWe report higher endoscopic colitis scores together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we show that topically administered insulin in inflamed colons of wildtype mice reduces inflammation-induced weight loss and improves remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores, reduced cyclooxygenase 2 mRNA expression, and developed significantly fewer and smaller tumors compared with the control group receiving phosphate-buffered saline only.

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 -