REVIEW article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
HMGB1: A Key Molecule Linking Chronic Inflammation to Complications in Type 2 Diabetes Mellitus and a Target for Exercise Intervention
1. Northwestern Polytechnical University, Xi'an, China
2. Beijing Sport University, Beijing, China
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Abstract
The pathological process of type 2 diabetes mellitus (T2DM) is closely associated with chronic low‑grade inflammation. High mobility group box 1 (HMGB1), a key damage‑associated molecular pattern (DAMP), is frequently dysregulated in T2DM and is implicated in promoting insulin resistance (IR), β cell dysfunction, and the progression of multiple complications—including cardiovascular disease, nephropathy, cognitive impairment, myopathy, and dyslipidemia— primarily through activating signaling pathways such as RAGE/TLR4‑NF‑κB. Exercise, a cornerstone non‑pharmacological intervention, effectively mitigates HMGB1‑driven pathology through multifaceted mechanisms. These include direct downregulation of HMGB1 expression and suppression of its downstream inflammatory pathways, as well as indirect effects via improved glycemic control, enhancing autophagy, and reduced oxidative stress. This review aims to systematically examine the evidence for the role of HMGB1 in T2DM pathogenesis and its complications, and to evaluate exercise as a potential strategy to target this inflammatory pathway, thereby providing a theoretical framework for future therapeutic approaches.
Summary
Keywords
diabetic complications, Exercise, HMGB1, Inflammation, T2DM
Received
17 December 2025
Accepted
16 February 2026
Copyright
© 2026 Fu, Xu and Gong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Lijing Gong
Disclaimer
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