Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2015; 21(44): 12593-12604
Published online Nov 28, 2015. doi: 10.3748/wjg.v21.i44.12593
Potential effect of chronic Helicobacter pylori infection on glucose metabolism of Mongolian gerbils
Zhen Yang, Wei Li, Cong He, Chuan Xie, Yin Zhu, Nong-Hua Lu
Zhen Yang, Wei Li, Cong He, Chuan Xie, Yin Zhu, Nong-Hua Lu, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Author contributions: Yang Z, Li W and He C contributed equally to this work; Yang Z and Lu NH designed the research; Li W, Xie C and Zhu Y performed the research; He C analyzed the data and wrote the paper.
Supported by (in part) grants from the National Natural Science Foundation of China, No. 81060038, No. 81270479, and No. 81470832; the National Science and Technology Major Projects for “Major New Drugs Innovation and Development” of China, No. 2011ZX09302-007-03; the “Talent 555 Project” of Jiangxi Province, China; and the Graduate Innovation Fund of Jiangxi Province, No. YC2014-B021.
Institutional review board statement: The study was reviewed and approved by the First Affiliated Hospital of Nanchang University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Nanchang University (2014-018).
Conflict-of-interest statement: The authors declare no conflict of interest.
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: Nong-Hua Lu, MD, Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Province, China. lunonghua@ncu.edu.cn
Telephone: +86-791-88692705 Fax: +86-791-88623153
Received: April 16, 2015
Peer-review started: April 18, 2015
First decision: May 18, 2015
Revised: June 19, 2015
Accepted: September 13, 2015
Article in press: September 14, 2015
Published online: November 28, 2015
Processing time: 224 Days and 15.9 Hours
Abstract

AIM: To assess the effect of Helicobacter pylori (H. pylori) infection on metabolic parameters in Mongolian gerbils.

METHODS: A total of 40 male, 5- to 8-wk-old, specific-pathogen-free Mongolian gerbils (30-50 g) were randomly allocated into two groups: a control group (n = 20) and an H. pylori group (n = 20). After a two-week acclimation period, the control group was administered Brucella broth and the H. pylori group was challenged intra-gastrically five times every other day with approximately 109/CFU H. pylori ATCC43504 (CagA+, VacA+). Each group was then divided into two subgroups, which were sacrificed at either 6 or 12 mo. The control and H. pylori subgroups each contained 10 Mongolian gerbils. Body weight, abdominal circumference, and body length were measured, and body mass index (BMI) and Lee’s index were calculated. Biochemical assays were used to detect serum indexes, including glucose, glycated hemoglobin (GHb), glycated hemoglobin A1c (HbA1c), triacylglycerol, and total cholesterol, using an automatic biochemistry analyzer. Inflammatory cytokines, including interleukin (IL)-1β, IL-2, IL-4, IL-10, IL-12, tumor necrosis factor-α (TNF-α) and interferon (IFN)-γ, were assayed using ELISA. The expression of insulin and insulin-like growth factor 1 (IGF-1) was detected by immunohistochemistry, and islet apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.

RESULTS: At each time point, body weight, abdominal circumference, BMI, and Lee’s index were increased after H. pylori infection. However, these differences were not significant. H. pylori infection significantly increased the GHb (5.45 ± 0.53 vs 4.98 ± 0.22, P < 0.05) and HbA1c (4.91 ± 0.61 vs 4.61 ± 0.15, P < 0.05) levels at 12 mo. We observed no significant differences in serum biochemical indexes, including fasting blood glucose, triacylglycerol and total cholesterol, at 6 or 12 mo after infection. H. pylori infection significantly increased the expression of IGF-1 (P < 0.05). Insulin levels from the pancreas and the apoptotic rate of islet β-cells remained unchanged. Also, we observed no significant differences among cytokines levels, including IL-1β, IL-2, IL-4, IL-10, IL-12, TNF-α and IFN-γ. IL-4 was the only exception, which increased at 6 (44.36 ± 25.17 vs 17.38 ± 3.47, P < 0.05) and 12 mo (33.41 ± 10.00 vs 18.91 ± 5.31, P < 0.05) after H. pylori infection.

CONCLUSION: Long-term H. pylori infection is significantly associated with high levels of HbA1c in Mongolian gerbils, indicating a potential role of H. pylori infection in glucose dysregulation.

Keywords: Helicobacter pylori; Glycated hemoglobin A1c; Glucose metabolism; Inflammatory cytokines

Core tip: Accumulating evidence suggests a link between Helicobacter pylori (H. pylori) infection and type 2 diabetes although it is controversial. This study assessed the effect of chronic H. pylori infection on metabolic parameters in Mongolian gerbils. The results showed that the glycated hemoglobin and glycated hemoglobin A1c levels increased significantly after H. pylori infection while no obvious differences of other serum indexes including fast glucose, lipid and cytokines were observed. It is assumed that chronic H. pylori infection might affect glucose metabolism and the inflammatory cytokines does not appear to mediate the effect. Further studies are warranted to elucidate the underlying mechanisms.