title: Oral insulin stimulates intestinal epithelial cell turnover following massive small bowel resection in a rat and a cell culture model.
abstract: OBJECTIVE
  We have recently reported that oral insulin (OI) stimulates intestinal adaptation after bowel resection and that OI enhances enterocyte turnover in correlation with insulin receptor expression along the villus-crypt axis. The purpose of the present study was to evaluate the effect of OI on intestinal epithelial cell proliferation and apoptosis in a rat model of short bowel syndrome (SBS) and in a cell culture model.
  
  
  METHODS
  Caco-2 cells were incubated with increasing concentrations of insulin. Cell proliferation and apoptosis were determined by FACS cytometry. Cell viability was investigated using the Alamar Blue technique. 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 third 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 bax and bcl-2 mRNA and western blotting was used to determine bax, bcl-2, p-ERK and AKT protein levels. Statistical analysis was performed using the one-way ANOVA test, with P < 0.05 considered statistically significant.
  
  
  RESULTS
  Treatment of Caco-2 cells with insulin resulted in a significant increase in cell proliferation (twofold increase after 24 h and 37% increase after 48 h) and cell viability (in a dose-dependent manner), but did not change cell apoptosis. In a rat model of SBS, treatment with OI resulted in a significant increase in all parameters of intestinal adaptation. Elevated cell proliferation rate in insulin treated rats was accompanied by elevated AKT and p-ERK protein levels. Decreased cell apoptosis in SBS-INS rats corresponded with a decreased bax/bcl-2 ratio.
  
  
  CONCLUSIONS
  Oral insulin stimulates intestinal epithelial cell turnover after massive small bowel resection in a rat model of SBS and a cell culture model.
authors: The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of intestinal adaptation and recovery, Haifa, Israel.
authors: Shani
authors: S
authors: Ben Lulu
authors: Arnold G
authors: AG
authors: Coran
authors: Naim
authors: N
authors: Shehadeh
authors: Raanan
authors: R
authors: Shamir
authors: Jorge G
authors: JG
authors: Mogilner
authors: Igor
authors: I
authors: Sukhotnik
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012778:Short Bowel Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D051028:bcl-2-Associated X Protein; D012313:RNA