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World J Diabetes. Oct 15, 2026; 17(10): 123730
Published online Oct 15, 2026. doi: 10.4239/wjd.123730
Published online Oct 15, 2026. doi: 10.4239/wjd.123730
Preventive carnosine supplementation attenuates painful diabetic neuropathy via restoring mitochondrial function and suppressing inflammasome activation
Zhuo-Ying Yu, Jing Yang, Ye Jiang, Yong-Zheng Han, Min Wei, Jia-Yin Shou, Shi-Xiong Shen, Yan-Han Lyu, Xin-Sheng Li, Xin-Ru Zhao, Min Li, Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China
Qian Chen, Department of Anesthesiology, Zhejiang University School of Medicine Children’s Hospital, Hangzhou 310052, Zhejiang Province, China
Guo-Gang Xing, Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Neuroscience Research Institute, Peking University, Beijing 100191, China
Da-Qing Ma, Department of Surgery and Cancer, Imperial College London, London SW10 9NH, United Kingdom
Co-first authors: Zhuo-Ying Yu and Jing Yang.
Co-corresponding authors: Da-Qing Ma and Min Li.
Author contributions: Yu ZY and Yang J jointly completed major experiments, data analysis and manuscript drafting, they contributed equally to this article, they are the co-first authors of this manuscript; Yu ZY, Yang J, Jiang Y, Han YZ, Wei M, Shou JY, Shen SX, Lyu YH, and Li XS performed the investigation; Yu ZY, Yang J, Han YZ, Shou JY, and Zhao XR curated and analyzed the data; Yu ZY drafted the original manuscript; Yu ZY, Yang J, Chen Q, Xing GG, Ma DQ, and Li M revised the manuscript; Yu ZY, Ma DQ, and Li M conceived the study and acquired funding; Ma DQ and Li M supervised the whole research project, interpreted research findings, repeatedly revised the manuscript and approved the final version, they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors have read and approved the final manuscript.
AI contribution statement: No artificial intelligence tools were utilized during the drafting, revision, data analysis or manuscript preparation process.
Supported by the National Natural Science Foundation of China, No. 82001329 and 82071411; the Beijing Municipal Natural Science Foundation, No. 7204325; the Key Research Foundation of Peking University Third Hospital, No. BYSYZD2019036; and the Special Fund of the National Clinical Key Specialty Construction Program, China (2025).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Peking University Third Hospital, approval No. 2022-111-01.
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: Technical appendix, statistical code, and datasets are available from the corresponding author at liminanesth@bjmu.edu.cn upon reasonable request.
Corresponding author: Min Li, MD, Chief Physician, Deputy Director, Professor, Department of Anesthesiology, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing 100191, China. liminanesth@bjmu.edu.cn
Received: June 2, 2026
Revised: July 8, 2026
Accepted: September 4, 2026
Published online: October 15, 2026
Processing time: 122 Days and 17.9 Hours
Revised: July 8, 2026
Accepted: September 4, 2026
Published online: October 15, 2026
Processing time: 122 Days and 17.9 Hours
Core Tip
Core Tip: Painful diabetic neuropathy (PDN) is characterized by impaired mitochondrial function and reduced carnosine levels in the dorsal root ganglia. Untargeted metabolomic analysis identified carnosine deficiency as a metabolic alteration associated with PDN. Preventive carnosine supplementation alleviated behavioral, electrophysiological, and mitochondrial abnormalities in diabetic rats and was associated with reduced dynamin-related protein 1-related mitochondrial fission and NOD-like receptor pyrin domain-containing protein 3 inflammasome activation in dorsal root ganglia. These findings were further supported by complementary in vitro experiments, collectively supporting further preclinical and translational evaluation of carnosine as a potential early-intervention strategy for PDN.