Wang Yingjie, Zhang Kexin, Zhang Xiaofei, Kan Chengxia, Sheng Sufang, Sun Xiaodong
Department of Endocrinology and Metabolism, Shandong Provincial Key Medical and Health Discipline of Endocrinology and Laboratory of Endocrinology and Metabolic Diseases, Clinical Research Center, Affiliated Hospital of Shandong Second Medical University, 261031, Weifang, China.
Mol Biol Rep. 2025 Sep 18;52(1):923. doi: 10.1007/s11033-025-11040-x.
Diabetes mellitus is a complex, chronic metabolic disease with a multifactorial pathogenesis involving genetic predisposition and environmental factors. Recently, epigenetics, particularly RNA methylation modifications, have gained increasing attention. N-methyladenosine (mA) is one of the most prevalent RNA modifications, and methyltransferase-like 3 (METTL3), the core component of the mA methyltransferase complex, plays a pivotal role in regulating key physiological and pathological processes, including islet β-cell function, insulin regulation, and glucose metabolism. This article reviews the mechanisms by which METTL3 and mA modifications contribute to the development of diabetes and its complications. Preclinical studies suggest METTL3 a promising target, but future research should focus on identifying safe, effective regulatory strategies for its clinical application. Overall, METTL3 and its mA-mediated modifications present promising novel therapeutic targets for the prevention and treatment of diabetes mellitus, providing novel theoretical insights and strategies for managing the disease and its complications.
糖尿病是一种复杂的慢性代谢性疾病，其发病机制多因素，涉及遗传易感性和环境因素。最近，表观遗传学，尤其是RNA甲基化修饰，受到了越来越多的关注。N6-甲基腺苷（m6A）是最普遍的RNA修饰之一，而m6A甲基转移酶复合体的核心成分甲基转移酶样3（METTL3）在调节关键的生理和病理过程中起关键作用，包括胰岛β细胞功能、胰岛素调节和葡萄糖代谢。本文综述了METTL3和m6A修饰导致糖尿病及其并发症发生的机制。临床前研究表明METTL3是一个有前景的靶点，但未来的研究应集中于确定其临床应用的安全、有效调控策略。总体而言，METTL3及其介导的m6A修饰为糖尿病的预防和治疗提供了有前景的新型治疗靶点，为管理该疾病及其并发症提供了新的理论见解和策略。
