Oral Insulin Enhances Intestinal Regrowth Following Massive Small Bowel Resection in Rat

Abstract

Experimental studies have suggested that insulin (INS) plays an important role in small intestinal growth and development. In the present study we investigated the effect of oral INS on structural intestinal adaptation and enterocyte proliferation and loss via apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-INS rats underwent bowel resection and were treated with oral INS given in the drinking water from the 3rd to the 15th postoperative day. Parameters of intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villous height, and crypt depth), enterocyte proliferation, and apoptosis were determined on day 15. SBS-INS rats demonstrated a significant increase (vs SBS rats) in jejunal and ileal overall bowel and mucosal weight, ileal mucosal DNA and protein, ileal villous height, and crypt depth. SBS-INS rats also showed an increased cell proliferation index in jejunum and ileum and decreased apoptotic index in jejunum compared to SBS animals. In conclusion, in a rat model of SBS, oral INS strongly enhances intestinal adaptation. Possible mechanisms may include increased cell proliferation and decreased enterocyte loss via apoptosis.

Effect of Oral Insulin on Diabetes-Induced Intestinal Mucosal Growth in Rats

“…Several in vitro and in vivo experiments have demonstrated that insulin and insulin-like growth factors enhance proliferation and diminish apoptosis in epithelial cells. We have previously observed similar effects of oral insulin on intestinal epithelial cell turnover in young rats after weaning [15], in rats after bowel resection [16] or adult rats after intestinal damage [17,18]. In contrast to these experiments, the current data suggest that OI supplementation in normal non-stressed adult rats exerts a mild inhibitory effect on microscopic intestinal mucosal parameters.…”

“…The insulin concentration of 1u/ml in drinking water had an optimal effect in this study. We have also demonstrated the positive trophic effects of OI on the small intestinal mucosa in certain gastrointestinal disorders, including short bowel syndrome [16], intestinal ischemia-reperfusion [17], and methotrexate-induced intestinal mucositis [18].…”

“…Group A-control rats (CONTR) were injected with vehicle and fed with regular chow diet; Group B-control rats were fed regular chow diet and water containing insulin at a concentration of 1u/1 ml as we described previously [15][16][17][18]; Group C-diabetic rats (DIAB) were injected with one dose of streptozotocin (STZ); Group D-DIAB-INS rats were injected with STZ and were treated with oral insulin similar to group B.…”

Dietary fenugreek seed extract improves performance and reduces fecal E. coli counts and fecal gas emission in lactating sows and suckling piglets

“…The improvement in nutrient and energy digestibility has been attributed to the saponin content in fenugreek seed that stimulate insulin activity, which in turn positively impacts intestinal morphology and therefore nutrient absorption (Sukhotnik et al 2005;Khalaji et al 2011). In the present study, the improvements in N and GE digestibility did not translate into improvements in any of the sow response criteria measured.…”

Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat

“…Since insulin has trophic gut effects, we hypothesized that insulin may have a beneficial effect on gut growth and recovery in different gastrointestinal disorders. We have recently demonstrated that oral insulin exerts a strong stimulating effect on bowel re-growth following massive small bowel resection in a rat [18]. In a different experiment, we have shown that oral insulin does not prevent ischemic damage but accelerates intestinal recovery, enhances enterocyte proliferation, and decreases cell death via apoptosis following intestinal ischemia-reperfusion in jury in rats [19].…”