Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2016; 22(23): 5353-5363
Published online Jun 21, 2016. doi: 10.3748/wjg.v22.i23.5353
Long-pulse gastric electrical stimulation protects interstitial cells of Cajal in diabetic rats via IGF-1 signaling pathway
Hai Li, Yan Chen, Shi Liu, Xiao-Hua Hou
Hai Li, Yan Chen, Shi Liu, Xiao-Hua Hou, Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Liu S conceived and designed the experiments; Li H and Chen Y performed the experiments; Li H analyzed the data; Liu S and Hou XH contributed reagents/materials/analytical tools; Li H wrote the paper; and Hou XH is the main controller of the laboratory.
Supported by National Natural Science Foundation of China, No. 81270458 and No. 81570488.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
Institutional animal care and use committee statement: All experiments involving animals were reviewed and approved by the Animal Care and Use Committee of Tongji Medical College, Huazhong University of Science and Technology (IACUC No. 488).
Conflict-of-interest statement: We declare that the authors of this article do not have any 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: Shi Liu, MD, Professor, Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China. shiliugao@yahoo.com
Telephone: +86-27-85726381 Fax: +86-27-85726930
Received: March 1, 2016
Peer-review started: March 3, 2016
First decision: April 1, 2016
Revised: April 14, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: June 21, 2016
Processing time: 103 Days and 22.3 Hours
Abstract

AIM: To investigate the effects of different parameters of gastric electrical stimulation (GES) on interstitial cells of Cajal (ICCs) and changes in the insulin-like growth factor 1 (IGF-1) signal pathway in streptozotocin-induced diabetic rats.

METHODS: Male rats were randomized into control, diabetic (DM), diabetic with sham GES (DM + SGES), diabetic with GES1 (5.5 cpm, 100 ms, 4 mA) (DM + GES1), diabetic with GES2 (5.5 cpm, 300 ms, 4 mA) (DM + GES2) and diabetic with GES3 (5.5 cpm, 550 ms, 2 mA) (DM + GES3) groups. The expression levels of c-kit, M-SCF and IGF-1 receptors were evaluated in the gastric antrum using Western blot analysis. The distribution of ICCs was observed using immunolabeling for c-kit, while smooth muscle cells and IGF-1 receptors were identified using α-SMA and IGF-1R antibodies. Serum level of IGF-1 was tested using enzyme-linked immunosorbent assay.

RESULTS: Gastric emptying was delayed in the DM group but improved in all GES groups, especially in the GES2 group. The expression levels of c-kit, M-SCF and IGF-1R were decreased in the DM group but increased in all GES groups. More ICCs (c-kit+) and smooth muscle cells (α-SMA+/IGF-1R+) were observed in all GES groups than in the DM group. The average level of IGF-1 in the DM group was markedly decreased, but it was up-regulated in all GES groups, especially in the GES2 group.

CONCLUSION: The results suggest that long-pulse GES promotes the regeneration of ICCs. The IGF-1 signaling pathway might be involved in the mechanism underlying this process, which results in improved gastric emptying.

Keywords: Long-pulse gastric electrical stimulation; Interstitial cells of Cajal; Gastric emptying; IGF-1 pathway; Diabetes mellitus; Gastrointestinal motility disorders

Core tip: Gastric electrical stimulation (GES) regulates gastric motility and protects the interstitial cells of Cajal (ICCs). However, the mechanisms underlying these processes have not been determined. In this study, we report that long-pulse GES with three different parameters protected ICCs and that the insulin-like growth factor 1 signaling pathway is probably involved in this process. One GES parameter (5.5 cpm, 300 ms, 4 mA) showed immense potential as a clinical application for applying long-pulse GES as the optimal parameter.