Electroacupuncture alleviates diabetic peripheral neuropathy: Regulates mitochondrial biogenesis and redistribution in peripheral nerve fibers

doi:10.4239/wjd.120935

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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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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Diabetes. Sep 15, 2026; 17(9): 120935
Published online Sep 15, 2026. doi: 10.4239/wjd.120935

Electroacupuncture alleviates diabetic peripheral neuropathy: Regulates mitochondrial biogenesis and redistribution in peripheral nerve fibers

Xuan Wang, Chong-Xi Yuan, Yun Liu, Wei-Feng Li, Meng-Jiang Lu, Tian-Cheng Xu, Zhi Yu, Bin Xu

Xuan Wang, College of Traditional Chinese Medicine, Jiangsu Medical College, Yancheng 224005, Jiangsu Province, China

Xuan Wang, Chong-Xi Yuan, Yun Liu, Meng-Jiang Lu, Tian-Cheng Xu, Zhi Yu, Bin Xu, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China

Chong-Xi Yuan, Department of Traditional Chinese Medicine, Suzhou Xiangcheng People’s Hospital, Suzhou 215100, Jiangsu Province, China

Wei-Feng Li, Yancheng Traditional Chinese Medicine Hospital, Yancheng 224000, Jiangsu Province, China

Co-first authors: Xuan Wang and Chong-Xi Yuan.

Co-corresponding authors: Zhi Yu and Bin Xu.

Author contributions: Wang X and Yuan CX contributed equally to this work as co-first authors; Wang X, Yuan CX, Liu Y, Li WF, Xu TC, Lu MJ, and Yu Z performed the animal experiments and collected the data; Wang X, Yuan CX, and Xu B analyzed and interpreted the data; Wang X drafted the manuscript; Wang X and Xu B supervised the study and contributed equally to this work as co-corresponding authors; all authors have read and approved the final manuscript.

Supported by the National Natural Science Foundation of China, No. 82405567, No. 82074532, No. 82374577, No. 82305375, No. 82305376, and No. 82505663; the Applied Basic Research Program of Yancheng, No. YCBK2025031; the Jiangsu Province Young Scientific and Technological Talents Promotion Plan, No. JSTJ-2025-890; and the Suzhou Science and Technology Innovation Project of Applied Basic Research (Medical and Health), No. SYW2024163.

Institutional review board statement: This study does not involve any human experiments.

Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals. All animal experimental procedures were conducted according to the guidelines for animal experimentation of the Nanjing University of Chinese Medicine and were approved by the Ethics Committee for Animal Experimentation (No. 202110A001).

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

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: No additional data are available.

Corresponding author: Bin Xu, MD, Doctor, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Road, Nanjing 210023, Jiangsu Province, China. xubin@njucm.edu.cn

Received: March 12, 2026
Revised: April 23, 2026
Accepted: June 17, 2026
Published online: September 15, 2026
Processing time: 173 Days and 1.3 Hours

Abstract

BACKGROUND

Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes, and current therapeutic options remain unsatisfactory. Mitochondrial dysfunction is considered a key contributor to DPN, and modulation of mitochondrial biogenesis may represent a promising therapeutic strategy. Electroacupuncture (EA) has shown beneficial effects in diabetic neuropathy, but its underlying mechanisms remain incompletely understood. We hypothesized that EA alleviates type 2 DPN (T2DPN) by enhancing silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)-mediated mitochondrial biogenesis and mitochondrial redistribution, particularly in intraepidermal nerve fibers (IENFs).

AIM

To investigate whether EA alleviates T2DPN through SIRT1/PGC-1α-mediated mitochondrial biogenesis and redistribution.

METHODS

A rat model of T2DPN was established by high-fat diet feeding combined with streptozotocin injection (35 mg/kg). After successful model establishment, rats received EA stimulation at ST25 for 6 weeks. Metabolic parameters, behavioral tests, nerve conduction studies, immunofluorescence staining, western blotting, and three-dimensional imaging were used to evaluate mitochondrial content and distribution in IENFs and sciatic nerve tissue, as well as SIRT1 and PGC-1α expression.

RESULTS

Changes in body weight, blood glucose, behavioral responses, and nerve conduction confirmed the successful establishment of the T2DPN model. EA improved metabolic status, increased withdrawal thresholds, and ameliorated IENF loss, indicating protective effects on neural function and morphology. In T2DPN rats, SIRT1/PGC-1α-mediated mitochondrial biogenesis was reduced. EA treatment upregulated SIRT1 and PGC-1α expression in the sciatic nerve and increased mitochondrial content. Three-dimensional analysis showed more prominent mitochondrial redistribution in IENFs than in adjacent keratinocytes. In addition, SIRT1 inhibition attenuated the beneficial effects of EA on nerve function, while showing limited effects on systemic metabolic parameters.

CONCLUSION

EA protects against T2DPN and is associated with SIRT1/PGC-1α-mediated mitochondrial biogenesis and redistribution, with neural benefits partly dissociated from metabolic regulation.

Keywords: Acupuncture; Diabetic peripheral neuropathy; Type 2 diabetes; Mitochondria distribution; Mitochondria biogenesis

Core Tip: Current treatments for diabetic peripheral neuropathy (DPN) remain limited, and new therapeutic strategies are needed. This study suggests that electroacupuncture (EA) exerts protective effects in type 2 DPN rats and may be associated with silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor-γ coactivator-1α-mediated mitochondrial biogenesis and mitochondrial redistribution, with more prominent changes observed in intraepidermal nerve fibers than in adjacent keratinocytes. Notably, inhibition of SIRT1 weakened the neural benefits of EA while having limited effects on systemic metabolic parameters, suggesting a partial dissociation between neural and metabolic effects.