Role of the Blood-Brain Barrier in Central Nervous System Insulin Resistance

The blood-brain barrier (BBB) mediates the communication between the periphery and the central nervous system (CNS). Recently, CNS insulin resistance has been elucidated to play a role in neurodegenerative disease. This has stimulated a wealth of information on the molecular impact of insulin in the brain, particularly in the improvement of cognition. Since the BBB regulates the transport of insulin into the brain and thus, helps to regulate CNS levels, alterations in the BBB response to insulin could impact CNS insulin resistance. In this review, we summarize the effect of insulin on some of the cell types that make up the BBB, including endothelial cells, neurons, astrocytes, and pericytes. We broadly discuss how these changes in specific cell types could ultimately impact the BBB. We also summarize how insulin can regulate levels of the pathological hallmarks of Alzheimer's disease, including amyloid beta (Aβ) and tau within each cell type. Finally, we suggest interventional approaches to overcome detrimental effects on the BBB in regards to changes in insulin transport.