Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies

文献类型： 外文期刊

第一作者： Meng, Xiangyuan

作者： Meng, Xiangyuan;Zhao, Zhenhu;Li, Siyao;Zhang, Xin;Guo, Ruihan;Liu, Huimin;Yuan, Yiling;Li, Wanrui;Song, Qi;Liu, Jinyu;Zhang, Hui

作者机构：

关键词： Alzheimer's disease; Type 3 diabetes mellitus; Insulin resistance; Metabolic reprogramming

期刊名称：MOLECULAR MEDICINE （ 影响因子：6.4； 五年影响因子：6.3 ）

ISSN： 1076-1551

年卷期： 2025 年 31 卷 1 期

页码：

收录情况： SCI

摘要： Abnormal glucose metabolism inevitably disrupts normal neuronal function, a phenomenon widely observed in Alzheimer's disease (AD). Investigating the mechanisms of metabolic adaptation during disease progression has become a central focus of research. Considering that impaired glucose metabolism is closely related to decreased insulin signaling and insulin resistance, a new concept "type 3 diabetes mellitus (T3DM)" has been coined. T3DM specifically refers to the brain's neurons becoming unresponsive to insulin, underscoring the strong link between diabetes and AD. Recent studies reveal that during brain insulin resistance, neurons exhibit mitochondrial dysfunction, reduced glucose metabolism, and elevated lactate levels. These findings suggest that impaired insulin signaling caused by T3DM may lead to a compensatory metabolic shift in neurons toward glycolysis. Consequently, this review aims to explore the underlying causes of T3DM and elucidate how insulin resistance drives metabolic reprogramming in neurons during AD progression. Additionally, it highlights therapeutic strategies targeting insulin sensitivity and mitochondrial function as promising avenues for the successful development of AD treatments.

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