Gene expression data from mouse colon. AOM+DSS induced colitis. INSR fl/fl mice or villin-CRE INSR-/- mice

The epithelial expression of the insulin receptor in the colon is previously reported to correlate with the extent of colonic inflammation. Here, we investigated the effect of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer. We report increased susceptibility to chemically-induced colitis 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 and developed significantly fewer and smaller tumors compared with the control group receiving phosphate-buffered saline only. Rectal insulin therapy can potentially be a novel treatment targeting the epithelial layer to enhance mucosal healing in the ulcerated areas. Our findings open up new possibilities for combination treatments to synergize with the existing anti-inflammatory therapies. 57 samples were analyzed. INSRfl/fl, untreated (10 biological replicates); INSRfl/fl AOM+DSS (10 biological replicates); villin-CRE INSR-/-, untreated (10 biological replicates); villin-CRE INSR-/- AOM+DSS (10 biological replicates), INSR fl/fl tumor AOM+DSS (8 biological replicates), villin-CRE INSR-/- tumor AOM+DSS (9 biological replicates)