Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis
Research output: Contribution to journal › Journal article › Research › peer-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 journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
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
C2 - 30137286
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