Exploring The Interconnected Pathways of Cognitive Decline and Type II Diabetes Mellitus: The Role of Glucose and Insulin Metabolism

Abstract: A person with Alzheimer’s disease and insulin resistance is unable to think clearly due to neurological dysfunction. Cognitive impairment is worsened by insulin resistance because insulin in neurons regulates glucose uptake and utilization, making neurons more functional. In insulin resistance, insulin cannot bind to its receptor, preventing neurons from receiving adequate nutrients. Insulin is transported across the blood–brain barrier via endothelial transport and GLUT transporters. The brain is a remarkable organ, requiring oxygen and other nutrients, and consuming about 40% of the body's minerals and energy. Our study highlights the similarities among the MAPK, PI3K/Akt, Notch signaling, and NLRP3 pathways, all of which are associated with Type 2 DM and AD. The brain, particularly the hippocampus, may be affected in patients with Type 2 diabetes; however, insulin resistance does not directly result from hippocampal injury. Numerous foundational biological studies examining the role of insulin in AD pathophysiology through cellular and molecular pathways support these findings. For example, insulin phosphorylates tau and activates glycogen synthase kinase 3β, contributing to the formation of neurofibrillary tangles. It is also notable that insulin is essential for the processing of the amyloid precursor protein.