Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat |
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Authors: | Igor Sukhotnik Naim Shehadeh Lilah Rothem Michael Lurie Jorge Mogilner Eitan Shiloni Raanan Shamir |
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Institution: | (1) Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb St, P.O. Box 4940, Haifa, 31048, Israel;(2) Department of Pediatrics, Meyer Children’s Hospital, Rambam Medical Center, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel;(3) Department of Pediatric Gastroenterology and Nutrition, Meyer Children’s Hospital, Rambam Medical Center, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel;(4) Department of Pathology, Bnai Zion Medical Center, Haifa, Israel;(5) Department of Surgery, Carmel Medical Center, Haifa, Israel |
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Abstract: | In the present study, we evaluated the protective effect of oral insulin (OI) on intestinal mucosa following lipopolysaccharide-induced intestinal damage in a rat. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats, LPS-rats that were treated with lipopolysaccharide (LPS), and LPS-INS rats that were treated with OI given in drinking water 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, enterocyte apoptosis, and mucosal expression of Toll-like receptor 4 (TLR4) were determined 24 h after the last LPS injection. LPS-INS animals showed a significantly greater bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, villus height in ileum, crypt depth in jejunum and ileum, cell proliferation rates in jejunum, and significantly lower apoptotic index in ileum compared to LPS- animals. LPS rats demonstrated 50% increase in TLR4 expression in jejunum compared to sham animals. Treatment with OI resulted in a three-fold increase in TLR4 expression in jejunum, compared to LPS animals. In conclusion, OI improves intestinal recovery after LPS endotoxemia in a rat. |
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Keywords: | Sepsis Lipopolysaccharide Oral insulin Intestine Mucosa |
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