Xu Fengqing, Shi Jingshan
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China.
Department of Pharmacology, in School of Pharmacy, Zunyi Medical University, Zunyi, China.
J Alzheimers Dis. 2025 Feb;103(4):994-1004. doi: 10.1177/13872877241307404. Epub 2025 Jan 10.
Type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) are two prevalent chronic diseases that pose significant global health challenges. Increasing evidence suggests a complex bidirectional relationship between these conditions, where T2D elevates the risk of AD, and AD exacerbates glucose metabolism abnormalities in T2D.
This review explores the molecular mechanisms linking T2D and AD, focusing on the role of insulin signaling pathways and oxidative stress.
A comprehensive literature search from PubMed, Web of Science, and other relevant databases was conducted and analyzed.
Insulin resistance in T2D leads to impaired insulin signaling in the brain, contributing to cognitive decline and the development of AD. Hyperglycemia-induced oxidative stress exacerbates neuronal damage, promoting the formation of amyloid-β plaques and neurofibrillary tangles characteristic of AD. Clinically antidiabetic drugs such as metformin show potential against AD in preclinical studies; Many natural products such as Lindl. have anti-T2D efficacy and are also effective against AD in various in vivo and in vitro models.
Improving insulin resistance and reducing oxidative stress are important strategies in the treatment of T2D and AD. To understand the bridging role of insulin singling and oxidative stress in T2D and AD will provide insights and broader applications in alleviating T2D and AD.
2型糖尿病（T2D）和阿尔茨海默病（AD）是两种常见的慢性疾病，给全球健康带来了重大挑战。越来越多的证据表明这两种疾病之间存在复杂的双向关系，即T2D会增加AD的风险，而AD会加剧T2D中的葡萄糖代谢异常。
本综述探讨了连接T2D和AD的分子机制，重点关注胰岛素信号通路和氧化应激的作用。
对来自PubMed、科学网和其他相关数据库进行了全面的文献检索和分析。
T2D中的胰岛素抵抗导致大脑中的胰岛素信号受损，导致认知能力下降和AD的发展。高血糖诱导的氧化应激会加剧神经元损伤，促进AD特有的淀粉样β斑块和神经原纤维缠结的形成。临床抗糖尿病药物如二甲双胍在临床前研究中显示出对AD的潜在作用；许多天然产物如石蒜等具有抗T2D功效，并且在各种体内和体外模型中对AD也有效。
改善胰岛素抵抗和降低氧化应激是治疗T2D和AD的重要策略。了解胰岛素信号和氧化应激在T2D和AD中的桥梁作用将为缓解T2D和AD提供见解和更广泛的应用。
