Zhang AY, Guo ZH, Huang Y, Shi YR, Song X, Wang SY, Yang GH, Liu Y, Xu TC. Vagal nerve innervation divergence in liver/pancreas: A forgotten key to endocrine recovery after transplantation? World J Transplant 2026; 16(2): 118169 [DOI: 10.5500/wjt.v16.i2.118169]
Corresponding Author of This Article
Tian-Cheng Xu, 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
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review-article
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Zhang AY, Guo ZH, Huang Y, Shi YR, Song X, Wang SY, Yang GH, Liu Y, Xu TC. Vagal nerve innervation divergence in liver/pancreas: A forgotten key to endocrine recovery after transplantation? World J Transplant 2026; 16(2): 118169 [DOI: 10.5500/wjt.v16.i2.118169]
Ao-Yun Zhang, Zi-Han Guo, Yuan Huang, Yu-Rou Shi, Xiao Song, Shuai-Yan Wang, Yun Liu, Tian-Cheng Xu, Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Guan-Hu Yang, Department of Specialty Medicine, Ohio University, Athens, OH 45701, United States
Co-first authors: Ao-Yun Zhang and Zi-Han Guo.
Co-corresponding authors: Yun Liu and Tian-Cheng Xu.
Author contributions: Zhang AY and Guo ZH conceptualized and designed this review; Zhang AY, Guo ZH, Huang Y, Shi YR, Wang SY and Song X wrote the first draft of the manuscript; all authors have reviewed and approved the final version of the manuscript; Zhang AY was responsible for the core conceptualization and overall framework, while Guo ZH was responsible for the creation of figures in the initial draft, both authors contributed significantly to the writing of the core content of the manuscript and coordinated the writing process, making essential and irreplaceable contributions to the completion of the project, and thus qualified as the co-first authors of the paper; Xu TC and Liu Y served as the corresponding authors, playing key roles in quality control, academic depth enhancement, and final manuscript coordination preparation as the co-corresponding authors; Xu TC and Yang GH focused on the academic depth and content rigor of the review, assuming key responsibilities for academic oversight, coordinating feedback from all authors on revised versions, leading responses to reviewer comments during the submission process, and guiding further improvements to the manuscript, ensuring the academic quality and publication standards of the review.
Supported by The National Natural Science Foundation, Youth Science Fund Project, 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 Talent Cultivation Program for Young Researchers, Key Laboratory of the Ministry of Education Project No. Zyqt202501 and No. Zyqt202503.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Tian-Cheng Xu, 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: December 26, 2025 Revised: January 18, 2026 Accepted: February 14, 2026 Published online: June 18, 2026 Processing time: 155 Days and 4.5 Hours
Abstract
As the cross talk of the parasympathetic nervous system, the vagus nerve exerts organ-specific regulatory effects on hepatic and pancreatic endocrine homeostasis, yet its divergent innervation patterns and their implications for post-transplant functional recovery remain understudied. This review summarizes the anatomical and functional differences of the vagus nerve in the liver and pancreas, and discusses how surgical denervation and incomplete re-innervation affect endocrine recovery after liver and pancreatic transplantation. At the anatomical level, vagus nerve fibers in the liver are relatively sparse and travel along the portal tripa, mainly terminating in the perihilar blood vessels and biliary tract ecological loci, with limited direct parenchymal synapses. This structure is conducive to metabolic perception and indirect regulation of liver glucose flux, bile acid-dependent signaling, and inflammatory tension. In contrast, pancreatic vagus nerve input enters through periarterial/periductal channels and is relays through pancreatic ganglia, forming dense cholinergic efferent control over pancreatic islet α/β/δ cells, supporting rapid and precise insulin-glucagon coordination and counterregulation responses. Clinically, recent preclinical trials and translational studies demonstrate that vagal nerve integrity-often compromised during transplant surgery-serves as a pivotal prognostic marker for endocrine recovery: Preserved vagal innervation is associated with accelerated glucose metabolism normalization and reduced post-transplant complications (e.g., insulin resistance, graft rejection). Notably, frontier strategies such as intraoperative vagal nerve-sparing techniques, targeted neuromodulation (e.g., vagus nerve stimulation), and stem cell-derived neurotrophic factor delivery have shown promising potential in mitigating denervation-induced endocrine dysfunction. This review emphasizes that deciphering the organ-specific vagal innervation mechanisms holds great promise for optimizing precision transplant surgery and developing novel neuromodulatory therapies, which may revolutionize the prognosis of liver and pancreatic transplant recipients.
Core Tip: The differences in vagal innervation between the liver and pancreas play an important role in the recovery of endocrine function after transplantation. Cutting-edge strategies such as intraoperative vagus nerve preservation techniques, targeted neuromodulation, and stem cell-derived neurotrophic factor delivery have shown new prospects for improving endocrine dysfunction after transplantation. Future research should focus on the organ-specific mechanisms of vagal innervation, and the development of novel neuromodulatory therapies is of great significance for transplant recipients.
