REVIEW article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Lactylation in Diabetes Mellitus and Its Complications: Mechanisms of Action and Therapeutic Potential - Recent Advances
Provisionally accepted
- Department of Endocrinology, Metabolism and Geriatrics, Guang'an People's Hospital, Guang'an, China
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Background: Diabetes mellitus (DM) and its complications represent a global health burden. Lactylation, a novel post-translational modification (PTM) linking metabolism to epigenetic regulation, has emerged as a key mediator in metabolic disorders. Objective: This review systematically summarizes the regulatory roles and therapeutic potential of lactylation in DM pathogenesis and complications. Key Findings: (1) Lactylation modulates core diabetic pathways by targeting IRS-1 (promoting insulin resistance), NLRP3 (amplifying inflammation), and FOXO1 (enhance oxidative stress); (2) Tissue-specific regulation is observed in complications: lactylation of LARS1 and ACSF2 exacerbates podocyte injury and mitochondrial dysfunction in nephropathy; the FTO-CDK2 axis drives vascular anomalies in retinopathy; and H4K12 lactylation activates Foxo1-mediated oxidative stress in cognitive impairment. Conclusion: Lactylation functions as a critical metabolic-epigenetic hub, and targeting its "writer-eraser-reader" system may offer novel therapeutic strategies for DM and complications, requiring further clinical translation.
Keywords: lactylation, Diabetes Mellitus, complications, post-translational modification, Metabolic-epigenetic regulation, therapeutic targets
Received: 22 Sep 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Zhou, Liu, Sun and Wang. 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: Xiaoshu Wang, 806880497@qq.com
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