Beneficial Effects of Oral Insulin on Intestinal Recovery Following Ischemia-Reperfusion Injury in Rat1
Authors: Raanan Shamir
Eitan Shiloni
Michael Lurie
Habib Helou
Naim Shehadeh
Igor Sukhotnik
Jorge Mogilner
Journal: Journal of Surgical Research (2005)
Discipline: CLINICAL MEDICINE
Keywords: oral insulin; ischemia-reperfusion; intestinal mucosal injury; rat; enterocyte proliferation
Affiliations: Department of Pediatric Surgery, B'nai Zion Medical Center, Haifa, Israel. 

Abstract:  Background: 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. Materials and methods: 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. Results: 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 &lt; 0.05) compared to IR-untreated animals. Conclusions: Oral insulin improves intestinal recovery after IR- injury in rat. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a set of at least 17 papers that appear to share immunohistochemistry images. All papers list Igor Sukhotnik as an author and they span a period of 14 years. The images do not always represent the same experiments. 1. Sukhotnik I et al., Pediatr Surg Int (2005) 21: 132u2013137, DOI: 10.1007 s00383-004-1308-2 2. Sukhotnik I et al., Journal of Surgical Research (2005), DOI: 10.1016 j.jss.2005.04.032 3. Sukhotnik I et al., Journal of Surgical Research (2007), DOI: 10.1016 j.jss.2007.02.002 4. Mogilner JG et al., Journal of Pediatric Surgery (2007), DOI: 10.1016 j.jpedsurg.2007.03.035 5. Sukhotnik I et al., Dig Dis Sci (2008), DOI: 10.1007 s10620-007-9990-2 6. Sukhotnik I et al., Cancer Biology Therapy (2009), DOI: 10.4161 cbt.8.10.8128 7. Sukhotnik I et al., Journal of Pediatric Surgery (2011), DOI: 10.1016 j.jpedsurg.2010.09.051 8. Ben-Lulu S et al., PLOS ONE (2012), DOI: 10.1371 journal.pone.0045221 9. Koppelman T et al., BMC Gastroenterology (2012), DOI: 10.1186 1471-230X-12-41 10. Koppelman T et al., British Journal of Nutrition (2013), DOI: 10.1017 S0007114512000542 11. Swaid F et al., Nutrition Metabolism (2013), DOI: 10.1186 1743-7075-10-53 12. Sukhotnik I et al., Nutrition Metabolism (2014), DOI: 10.1186 1743-7075-11-17 13. Sukhotnik I et al., PLOS ONE (2014), DOI: 10.1371 journal.pone.0110675 14. Sukhotnik I et al., European Journal of Pediatric Surgery (2016), DOI: 10.1055 s-0036-1587588 15. Ben Shahar Y et al., European Journal of Pediatric Surgery (2016), DOI: 10.1055 s-0035-1559886 16. Sukhotnik I et al., Food Nutrition Research (2018), DOI: 10.29219 fnr.v62.1327 17. Ben-Shahar Y et al., European Journal of Pediatric Surgery (2019), DOI: 10.1055 s-0039-1700550 Here are four collages of the IHC figures from these papers, with boxes of the same color highlighting panels that look more similar than expected. * Collage 1: ![file] * Collage 2: ![file] * Collage 3: ![file] * Collage 4: ![file] , 
 Could the authors please comment on a potential conflict of interest between this paper and a provisional patent application? U.S. Provisional Patent Application No. 60 575,803 was filed on June 2, 2004, and later replaced by PCT Patent Application No. PCT IL2005 000587, filed on June 2 2005, as per https: patents.google.com patent US8026211B2 en From the invention:  A method for increasing intestinal function is provided. The method comprising orally and or enterally administering to a subject in need thereof a therapeutically effective amount of insulin, thereby increasing intestinal function (...) The present invention relates to methods and formulations for increasing intestinal function, which may be used for treating short bowel syndrome. ,