Differential effects of RYGB surgery and best medical treatment for obesity-diabetes on intestinal and islet adaptations in obese-diabetic ZDSD rats

Ananyaa Sridhar, Dawood Khan, Mahmoud Abdelaal, Jessie A. Elliott, Violetta Naughton, Peter R. Flatt, Carel W. Le Roux, Neil G. Docherty, Charlotte R. Moffett, Jo Edward Lewis (Editor)

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Modification of gut-islet secretions after Roux-En-Y gastric bypass (RYBG) surgery contributes to its metabolic and anti-diabetic benefits. However, there is limited knowledge on tissue-specific hormone distribution post-RYGB surgery and how this compares with best medical treatment (BMT). In the present study, pancreatic and ileal tissues were excised from male Zucker-Diabetic Sprague Dawley (ZDSD) rats 8-weeks after RYGB, BMT (daily oral dosing with metformin 300mg/kg, fenofibrate 100mg/kg, ramipril 1mg/kg, rosuvastatin 10mg/kg and subcutaneous liraglutide 0.2mg/kg) or sham operation (laparotomy). Insulin, glucagon, somatostatin, PYY, GLP-1 and GIP expression patterns were assessed using immunocytochemistry and analyzed using ImageJ. After RYGB and BMT, body weight and plasma glucose were decreased. Intestinal morphometry was unaltered by RYGB, but crypt depth was decreased by BMT. Intestinal PYY cells were increased by both interventions. GLP-1- and GIP-cell counts were unchanged by RYGB but BMT increased ileal GLP-1-cells and decreased those expressing GIP. The intestinal contents of PYY and GLP-1 were significantly enhanced by RYGB, whereas BMT decreased ileal GLP-1. No changes of islet and beta-cell area or proliferation were observed, but the extent of beta-cell apoptosis and islet integrity calculated using circularity index were improved by both treatments. Significantly decreased islet alpha-cell areas were observed in both groups, while beta- and PYY-cell areas were unchanged. RYGB also induced a decrease in islet delta-cell area. PYY and GLP-1 colocalization with glucagon in islets was significantly decreased in both groups, while co-staining of PYY with glucagon was decreased and that with somatostatin increased. These data characterize significant cellular islet and intestinal adaptations following RYGB and BMT associated with amelioration of obesity-diabetes in ZDSD rats. The differential responses observed and particularly those within islets, may provide important clues to the unique ability of RYGB to cause diabetes remission.
Original languageEnglish
Article numbere0274788
Pages (from-to)e0274788
Number of pages21
JournalPLoS ONE
Issue number9
Early online date22 Sept 2022
Publication statusPublished (in print/issue) - 22 Sept 2022

Bibliographical note

Publisher Copyright:
© 2022 Sridhar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • Research Article
  • Biology and life sciences
  • Medicine and health sciences
  • Physical sciences
  • Gastric Bypass
  • Blood Glucose/metabolism
  • Glucagon-Like Peptide 1/metabolism
  • Liraglutide/pharmacology
  • Rats
  • Rosuvastatin Calcium
  • Male
  • Ramipril
  • Somatostatin/therapeutic use
  • Diabetes Mellitus
  • Glucagon/metabolism
  • Rats, Sprague-Dawley
  • Fenofibrate
  • Rats, Zucker
  • Animals
  • Insulin/metabolism
  • Obesity/surgery
  • Metformin


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