Insulin signaling and oxidative stress: Bridging the gap between type 2 diabetes mellitus and Alzheimer's disease

Background 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. Objective This review explores the molecular mechanisms linking T2D and AD, focusing on the role of insulin signaling pathways and oxidative stress. Methods A comprehensive literature search from PubMed, Web of Science, and other relevant databases was conducted and analyzed. Results 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 Dendrobium nobile Lindl. have anti-T2D efficacy and are also effective against AD in various in vivo and in vitro models. Conclusions 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.