Oral insulin up-regulates Toll-like receptor 4 expression and enhances intestinal recovery following lipopolysaccharide-induced gut injury in a rat
Authors: Raanan Shamir
Eitan Shiloni
Michael Lurie
Naim Shehadeh
Igor Sukhotnik
Jorge Mogilner
Lilah Rothem
Journal: Digestive Diseases and Sciences (2008)
Discipline: CLINICAL MEDICINE
Keywords: oral insulin; intestinal mucosa; lipopolysaccharide; rat; protective effect
Affiliations: Department of Pediatric Surgery B, Bnai Zion Medical Center, Haifa, Israel. 

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. 

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. ,