Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2017; 23(19): 3468-3479
Published online May 21, 2017. doi: 10.3748/wjg.v23.i19.3468
Diabetes recurrence after metabolic surgeries correlates with re-impaired insulin sensitivity rather than beta-cell function
Teng Liu, Ming-Wei Zhong, Yi Liu, Dong Sun, Meng Wei, Xin Huang, Yu-Gang Cheng, Qun-Zheng Wu, Dong Wu, Xiao-Qian Zhang, Ke-Xin Wang, San-Yuan Hu, Shao-Zhuang Liu
Teng Liu, Ming-Wei Zhong, Dong Sun, Meng Wei, Xin Huang, Yu-Gang Cheng, Qun-Zheng Wu, Dong Wu, Xiao-Qian Zhang, Ke-Xin Wang, San-Yuan Hu, Shao-Zhuang Liu, Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Yi Liu, Health and Family Planning Commission of Shandong Provincial Medical Guidance Center, Jinan 250012, Shandong Province, China
Author contributions: Liu T, Hu SY and Liu SZ designed the study and wrote the manuscript; Liu T and Zhong MW instructed on the whole study and prepared the figures; Liu Y and Wang KX collected and analyzed the data; Sun D, Wei M, Huang X and Cheng YG performed the operations and performed the observational study; Wu QZ, Wu D, Zhang XQ performed the molecular investigations; and all authors have approved the final version to be published.
Supported by National Natural Science Foundation of China, No. 81300286 to Liu SZ and No. 81471019 to Hu SY; Foundation for Outstanding Young Scientist in Shandong Province, No. BS2013YY031 to Liu SZ; Science and Technology Development Program of Shandong Province, No. 2014GGE27485 to Liu SZ; Specialized Research Fund for the Doctoral Program of Higher Education of China, No. 20130131120069 to Liu SZ.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Qilu Hospital of Shandong University, Jinan, China.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee on Animal Experiment of Shandong University Qilu Hospital (IACUC protocol number: DWLL-2015-014).
Conflict-of-interest statement: All authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shao-Zhuang Liu, MD, PhD, Department of General Surgery, Qilu Hospital of Shandong University, No. 107, Wenhua Xi Road, Jinan 250012, Shandong Province, China. liushaozhuang@sdu.edu.cn
Telephone: +86-531-86920598 Fax: +86-531-86920598
Received: January 20, 2017
Peer-review started: January 20, 2017
First decision: February 9, 2017
Revised: April 25, 2017
Accepted: May 4, 2017
Article in press: May 4, 2017
Published online: May 21, 2017
Processing time: 119 Days and 19.2 Hours
Abstract
AIM

To investigate factors causing diabetes recurrence after sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB).

METHODS

SG and DJB were performed on rats with diabetes induced by high-fat diet (HFD) and streptozotocin (STZ). HFD was used to induce diabetes recurrence at 4 wk postoperatively. Body weight, oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), insulin signaling [IR, insulin receptor substrate (IRS)1, IRS2, phosphatidylinositol 3-kinase and AKT in liver and skeletal muscle], oral glucose stimulated insulin secretion, beta-cell morphology (mass, apoptosis and insulin secretion), glucagon-like peptide (GLP)-1, PYY and ghrelin were compared among SG rats with common low-fat diet (SG-LFD), SG with HFD (SG-HFD), DJB rats with LFD (DJB-LFD), DJB with HFD (DJB-HFD) and sham-operation with LFD (Sham) at targeted postoperative times.

RESULTS

SG and DJB resulted in significant improvement in glucose tolerance, lower HOMA-IR, up-regulated hepatic and muscular insulin signaling, higher levels of oral glucose-stimulated insulin secretion, bigger beta-cell mass, higher immunofluorescence intensity of insulin, fewer transferase-mediated dUTP-biotin 3’ nick end-labeling (TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group. The improvement in glucose tolerance was reversed at 12 wk postoperatively. Compared with the SG-LFD and DJB-LFD groups, the SG-HFD and DJB-HFD groups showed higher HOMA-IR, down-regulated hepatic and muscular insulin signaling, and more TUNEL-positive beta cells. No significant difference was detected between HFD and LFD groups for body weight, glucose-stimulated insulin secretion, beta-cell mass, immunofluorescence intensity of insulin, and postprandial GLP-1 and PYY levels. Fasting serum ghrelin decreased in SG groups, and there was no difference between HFD-SG and LFD-SG groups.

CONCLUSION

HFD reverses the improvement in glucose homeostasis after SG and DJB. Diabetes recurrence may correlate with re-impaired insulin sensitivity, but not with alterations of beta-cell function and body weight.

Keywords: Apoptosis; Diabetes recurrence; Duodenal-jejunal bypass; Pancreatic beta cell; Sleeve gastrectomy

Core tip: To investigate factors causing diabetes recurrence after sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB), we performed SG and DJB on diabetic rats and high-fat diet was used to induce diabetes recurrence at 4 wk postoperatively. The result showed that diabetes recurrence may correlate with re-impaired insulin sensitivity, but not with alterations of beta-cell function and body weight.