Beneficial Effects of Oral Insulin on Intestinal Recovery Following Ischemia-Reperfusion Injury in Rat 1

Abstract

It has been reported that oral insulin has a trophic effect on intestinal mucosa, but the precise mechanism of its action is still unclear. The purpose of the present study was to investigate the effect of oral insulin on ischemia-reperfusion (IR) intestinal mucosal injury in rat. Male Sprague-Dawley rats underwent laparotomy (Sham) or IR-intestinal damage by clamping both the superior mesenteric artery and the portal vein for 30 min followed by 24 h reperfusion. IR-INS rats were treated with oral insulin given in drinking water (1U/ml) 48 h before and after IR. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h after IR. Park's score was used for the quantitative assessment of histological change. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P less than 0.05 considered statistically significant. IR-injury resulted in a significant decrease in bowel weight in jejunum, mucosal weight in jejunum and ileum, villus height in jejunum and ileum, cell proliferation index in jejunum, and ileum compared to sham animals. IR-INS animals demonstrated greater duodenal and jejunal bowel weight, duodenal, jejunal and ileal mucosal weight, jejunal mucosal DNA, jejunal and ileal mucosal protein, jejunal and ileal villus height and crypt depth, jejunal and ileal proliferation index compared to IR-animals. Oral insulin administration induced also a significant decrease in apoptotic index in ileum (1.2 +/- 0.4 versus 2.8 +/- 0.7 TUNEL positive cells/10 villi, P < 0.05) compared to IR-untreated animals. Oral insulin improves intestinal recovery after IR- injury in rat.