Grant: Project Grant

Insulin is a hormone essential for life. It is best known for its effect on the regulation of blood sugar levels; the reason why it is an essential player in the pharmaceutical treatment of diabetes. It is increasingly recognized that insulin in the blood also affects the brain. For example, insulin is under clinical trial in Alzheimer's disease, because studies show it improves memory. However, between the blood and the brain stands what we call the "blood-brain barrier" or BBB. The BBB is mainly composed of highly active cells called "endothelial cells", which basically control everything that goes in the brain or that goes out. Although small quantities of insulin are generated in the brain, the vast majority is produced by the pancreas and secreted in the bloodstream. Therefore, to interact with brain cells, blood insulin must first interact with the BBB. Surprisingly enough, how exactly insulin interacts with the BBB remains relatively unknown. Although it is clear that insulin must interact with its receptor located on the BBB, we don't know much of what happens next. The purpose of the present grant application is to better understand how blood insulin (i) is transported into the brain, (ii) stimulates BBB endothelial cells to carry metabolic information into the brain, (iii) changes brain function and behavior. We expect that answering these questions will be extremely useful for treating not only diabetes, but also Alzheimer's disease. For example, we recently found that neurotoxic amyloid peptides are washed out of the brain into the bloodstream within minutes after an injection of insulin, suggesting that insulin-related mechanisms can be used to treat this terrible disease. In summary, we hope that the present proposal will contribute to develop new drugs that will benefit both diabetes and Alzheimer's disease patients.