Electroacupuncture protects gastric Cajal cells by reducing macrophage pyroptosis in diabetic gastroparesis

doi:10.4239/wjd.v17.i2.114252

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Diabetes. Feb 15, 2026; 17(2): 114252
Published online Feb 15, 2026. doi: 10.4239/wjd.v17.i2.114252

Electroacupuncture protects gastric Cajal cells by reducing macrophage pyroptosis in diabetic gastroparesis

Ming-Wei Fan, Jin-Lan Tian, Shu-Hui Zhang, Zi-Jian Zhao, Xin-Ru Liu, Cheng-Xia Liu, Yan Chen

Ming-Wei Fan, Jin-Lan Tian, Shu-Hui Zhang, Zi-Jian Zhao, Xin-Ru Liu, Yan Chen, Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256603, Shandong Province, China

Cheng-Xia Liu, Department of Gastroenterology and Hepatology, Binzhou Medical University Hospital, Binzhou 256603, Shandong Province, China

Co-first authors: Ming-Wei Fan and Jin-Lan Tian.

Co-corresponding authors: Cheng-Xia Liu and Yan Chen.

Author contributions: Fan MW and Tian JL made equal contributions as co-first authors; Tian JL conducted animal experimentation studies; Fan MW assessed the gastrointestinal motility in rats and authored the manuscript; Zhao ZJ administered drug injections to the rats; Liu XR conducted measurements of the animals’ blood glucose levels and body weights; Zhang SH directed the animal experiments; Chen Y and Liu CX provided the study design and methodological suggestions, and discussed the data. All authors approved the final version to publish.

Institutional animal care and use committee statement: The Animal Protection and Use Committee has formally approved all experimental protocols, No. 20250107-05.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The datasets utilized in this study can be obtained from the corresponding author upon reasonable request.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Yan Chen, PhD, Department of Gastroenterology, Binzhou Medical University Hospital, No. 661 Yellow River Second Road, Bincheng District, Binzhou 256603, Shandong Province, China. chenyanfeihong0906@163.com

Received: September 15, 2025
Revised: October 11, 2025
Accepted: December 16, 2025
Published online: February 15, 2026
Processing time: 144 Days and 22 Hours

Abstract

BACKGROUND

This study elucidates the mechanisms through which electroacupuncture (EA) at Zusanli acupoint, applied at different frequencies, alleviates diabetic gastroparesis (DGP). The modulation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, its regulation of M2 macrophage pyroptosis, and the consequent protection of interstitial cells of Cajal (ICCs) were investigated.

AIM

To investigate the mechanism by which EA alleviates DGP.

METHODS

A DGP rat model was induced by feeding a high-fat/high-sucrose diet combined with a single intraperitoneal injection of streptozotocin (30 mg/kg). Rats successfully modeled were randomly assigned into four groups (n = 6 each): Untreated DGP, sham-EA (0 Hz, 0 mA), low-frequency EA (LEA, 10 Hz, 1-3 mA), and high-frequency EA (HEA, 100 Hz, 1-3 mA). EA was delivered at Zusanli acupoint for 60 minutes daily over 8 weeks. Gastric emptying rate and whole gut transit time were evaluated. Gastric antrum tissues were examined by immunofluorescence and western blotting to assess ICC integrity, M2 macrophage distribution, pyroptosis-related markers (Gasdermin D, NOD-like receptor family pyrin domain containing 3, caspase-1), inflammatory cytokines [interleukin (IL)-1β, IL-18], and cGAS-STING signaling proteins.

RESULTS

The results of this study revealed that HEA significantly increased gastric emptying [0.69 (0.55, 0.72) vs DGP 0.44 (0.26, 0.48), P < 0.05] and reduced whole gut transit time (361.34 ± 10.51 vs DGP 537.33 ± 100.57, P < 0.01), with improved efficacy compared to LEA. In DGP rats, ICC counts were significantly reduced, transferase dUTP nick-end labeling-positive apoptotic markers were elevated, and CD206+ cells were diminished; these alterations were reversed mainly by EA, with HEA showing the greatest effect. Expression of cGAS-STING signaling components and pyroptosis-related proteins (Gasdermin D, NOD-like receptor family pyrin domain containing 3, caspase-1), along with secretion of IL-1β and IL-18, were significantly up-regulated in the DGP group. HEA significantly suppressed cGAS pathway activation, reduced pyroptosis-associated proteins and inflammatory mediators, and outperformed LEA (P < 0.05).

CONCLUSION

HEA ameliorates gastric dysmotility in DGP by suppressing the cGAS-STING pathway, attenuating M2 macrophage pyroptosis and inflammatory responses, and preserving ICC networks. These findings identify a novel EA/cGAS-STING/pyroptosis axis and highlight its therapeutic potential as a mechanistic target for optimizing DGP treatment strategies.

Keywords: Diabetic gastroparesis; Interstitial cells of Cajal; Pyroptosis; Macrophages; Electroacupuncture

Core Tip: For the first time we show that high-frequency electroacupuncture at Zusanli acupoint outperforms low-frequency stimulation in diabetic gastroparesis by simultaneously blocking the cyclic GMP-AMP synthase-stimulator of interferon genes pathway, halting M2-macrophage pyroptosis, curtailing interleukin-1β/interleukin-18 release and thereby rescuing the interstitial cells of Cajal network, offering an immediately translatable, non-drug strategy to restore gastric motility.