Diabetes and Brain

Abstract

The term "brain diabetes or type 3 diabetes" has begun to be used by researchers targeting the possible link between AD and T2 diabetes mellitus (DM). The main reason for using this term is to emphasize the common neurodegenerative mechanisms with AD and diabetes and the importance of brain In-Res. Insulin dysregulation and advanced glycation end products (AGEs) can be considered as the main associated factors for the disruption of glucose homeostasis and the pathophysiology of AD. AGE accumulation increases Aβ-42 formation via oxidative stress, NF-κβ activation, upregulation of BACE1, PSEN1 and γ-secretase, and mitochondrial dysfunction. In addition, the presence of insulin receptors and insulin signalling pathways identified in different brain regions indicates the important physiological (neurodevelopment, feeding behaviour, etc.) and cognitive (attention, learning and memory, etc.) effects of insulin on the brain, and in a way, emphasizes that the brain is an insulin-sensitive organ. The simultaneous occurrence of insulin-related CNS and systemic dysregulation in the early stages of AD suggests that these two diseases are inextricably linked. Hypometabolism, which develops as a result of insulin signalling pathway disruption, is among the altered bioenergetic parameters that associate T2DM with AD. In-Res in AD&DM cause hyperinsulinemia, leading to insulin and Aβ build up and insulin-degrading-enzyme saturation. However, when insulin levels rise, as seen in T2DM, insulin competes for insulin-degrading-enzyme, leading to reduced Aβ degradation and its subsequent accumulation in neurons. Dysfunctional insulin pathways and In-Res are characterized by receptor dysfunction, changed expression levels, poor binding, and defective events in the phosphorylation cascade. Overall, poor insulin signalling may result in altered cerebral metabolism, which can contribute to brain dysfunction, providing potential explanations for the relationship between DM&AD.