Wang SY, Liu X, Li ZM, Deng CX, Chen KR, Zhuang SY, Xu B, Xu TC. Peripheral nerve-mediated glucose lowering: Mechanisms, translational strategies, and future perspectives. World J Diabetes 2026; 17(1): 114535 [DOI: 10.4239/wjd.v17.i1.114535]
Corresponding Author of This Article
Tian-Cheng Xu, MD, PhD, Professor, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, Jiangsu Province, China. xtc@njucm.edu.cn
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
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/
Shuai-Yan Wang, Xin Liu, Zi-Mu Li, Chen-Xi Deng, Ke-Ran Chen, Si-Yu Zhuang, Bin Xu, Tian-Cheng Xu, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Co-first authors: Shuai-Yan Wang and Xin Liu.
Co-corresponding authors: Bin Xu and Tian-Cheng Xu.
Author contributions: Wang SY and Liu X contribute equally to this study as co-first authors; Xu B and Xu TC contribute equally to this study as co-corresponding authors; Wang SY was responsible for the idea and conceptual framework; Wang SY, Liu X, Li ZM, Deng CX, Chen KR, Zhuang SY wrote the first draft of the manuscript; Xu TC and Xu B reviewed the manuscript and critically revised it for important intellectual content; all authors have reviewed and approved the final version of the manuscript.
Supported by The National Natural Science Foundation, No. 82305376; The Youth Talent Support Project of the China Acupuncture and Moxibustion Association, No. 2024-2026ZGZJXH-QNRC005; The 2024 Jiangsu Province Youth Science and Technology Talent Support Project, No. JSTJ-2024-380; and 2025 Jiangsu Provincial Science and Technology Think Tank Program Project, No. JSKX0125035.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest associated with the publication of this manuscript.
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: Tian-Cheng Xu, MD, PhD, Professor, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, Jiangsu Province, China. xtc@njucm.edu.cn
Received: September 23, 2025 Revised: October 23, 2025 Accepted: November 19, 2025 Published online: January 15, 2026 Processing time: 114 Days and 0 Hours
Abstract
Glucose homeostasis is crucial for metabolic health, with disruptions leading to hyperglycemia (e.g., diabetes affecting over 589 million adults worldwide in 2025) or hypoglycemia, both associated with severe complications like nephropathy, neuropathy, and cardiovascular disease. The peripheral nervous system (PNS) is a less studied regulator of glucose balance through neural circuits involving the sympathetic, parasympathetic, sensory, and somatic nerves, which interact with organs like the liver, pancreas, and gut. This review aims to synthesize recent advances in PNS-mediated glucose lowering, covering mechanistic foundations, organ-specific pathways, translational interventions (e.g., device-based neuromodulation, pharmacological approaches, closed-loop systems, and regenerative strategies), preclinical/clinical evidence, translational challenges, and future perspectives to provide a roadmap for developing novel, drug-free therapies for dysglycemia.
Core Tip: The peripheral nervous system is an underappreciated regulator of glucose balance. Targeted neuromodulation, like vagus nerve stimulation or focused ultrasound, modulates neural circuits to control liver glucose output, pancreatic hormones, and tissue uptake. Preclinical data show strong metabolic gains; early human trials prove safety. Tackling issues in precision, patient differences, and nerve damage could enable scalable, drug-free treatments for diabetes.
