A historical perspective on the interactions of insulin at the blood-brain barrier

Subsequent to the discovery of insulin in 1921, the role of insulin in the brain has been investigated throughly. The ability of insulin to act within the brain to regulate peripheral glucose levels helped evolve the research surrounding the ability of insulin to be transported into the brain. Investigations aiming to determine the transport of insulin into the brain from the circulation soon followed. Once it was established that insulin could enter the brain, the ability of insulin to bind brain microvessels and regulators of this process were determined. As technology advanced, quantitative measurements to specify the transport rate of insulin across the blood-brain barrier (BBB) and the impact of physiological conditions and diseases were the logical next steps. Lastly, with the advent of genetic mouse models and high-specificity antagonists, the specific role of the insulin receptor in mediating insulin transport could begin to be explored. In this review, we summarise the main findings throughout the decades regarding the interactions of insulin at the BBB.