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.
OBJECTIVE
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 < 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.
Laboratory of Intestinal Adaptation and Recovery, Technion-Israel Institute of Technology, The Ruth & Bruce Rappaport Faculty of Medicine, Haifa, Israel.
Shani
S
Ben Lulu
Arnold G
AG
Coran
Jorge G
JG
Mogilner
Ron
R
Shaoul
Raanan
R
Shamir
Naim
N
Shehadeh
Igor
I
Sukhotnik
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007328:Insulin / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D011972:Receptor, Insulin