Oral insulin stimulates intestinal epithelial cell turnover in correlation with insulin-receptor expression along the villus–crypt axis in a rat model of short bowel syndrome
Authors: Raanan Shamir
Arnold G Coran
Shani Ben Lulu
Ron Shaoul
Naim Shehadeh
Igor Sukhotnik
Jorge G Mogilner
Journal: Pediatric Surgery International (2010)
Discipline: CLINICAL MEDICINE
Keywords: oral insulin; intestinal mucosa; enterocyte turnover; insulin-receptor expression; rat model
Affiliations: Laboratory of Intestinal Adaptation and Recovery, Technion-Israel Institute of Technology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel.

Abstract:  Purpose: It has been reported that oral insulin (OI) has a trophic effect on intestinal mucosa. In the present study, we evaluated the effect of OI on enterocyte turnover and correlated it with insulin-receptor expression along the villus-crypt axis in a rat model of short bowel syndrome (SBS). Methods: Male rats were divided into three groups: Sham rats underwent bowel transection, SBS rats underwent a 75% bowel resection, and SBS-OI rats underwent bowel resection and were treated with OI given in drinking water (1 U/ml) from the fourth postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Real-time PCR was used to determine the level of insulin receptor-beta (IRB) mRNA. Insulin-receptor expression along the villus-crypt axis (villus tips, lateral villi and crypts) was assessed by immunohistochemistry. The effect of OI on cell turnover for each compartment was evaluated in correlation with the receptor expression. Statistical analysis was performed using the one-way ANOVA test, with P &lt; 0.05 considered statistically significant. Results: Treatment with OI resulted in a significant increase in all parameters of intestinal adaptation. Insulin-receptor expression in crypts significantly increased in SBS rats (vs. Sham rats) and was accompanied by a significant increase in enterocyte proliferation following OI administration. A significant increase in insulin-receptor expression at the tip of the villous and in the lateral villous in SBS rats (vs. Sham) was accompanied by decreased cell apoptosis in these compartments following treatment with OI. Conclusions: In a rat model of SBS, OI enhances enterocyte turnover and stimulates intestinal adaptation. The stimulating effect of insulin on enterocyte turnover correlates with insulin-receptor expression along the villus-crypt axis. 

Retracted: No

PubPeer comments:
 Could the authors please comment on a potential conflict of interest between this paper and a provisional patent application? U.S. Provisional Patent Application No. 60 575,803 was filed on June 2, 2004, and later replaced by PCT Patent Application No. PCT IL2005 000587, filed on June 2 2005, as per https: patents.google.com patent US8026211B2 en From the invention:  A method for increasing intestinal function is provided. The method comprising orally and or enterally administering to a subject in need thereof a therapeutically effective amount of insulin, thereby increasing intestinal function (...) The present invention relates to methods and formulations for increasing intestinal function, which may be used for treating short bowel syndrome. I cannot find any statement about a potential conflict of interest in this paper. ,