Routes for the delivery of insulin to the central nervous system: A comparative review

Central nervous system (CNS) insulin resistance is a condition in which the cells within the CNS do not respond to insulin appropriately and is often linked to aberrant CNS insulin levels. CNS insulin is primarily derived from the periphery. Aberrant CNS insulin levels can arise due to various factors including i) decreased endogenous insulin transport into the brain, across the blood-brain barrier (BBB), ii) reduced CNS sequestration of insulin, and iii) increased CNS degradation. While the sole route of endogenous insulin transport into the brain is via the BBB, there are multiple therapeutic routes of administration that have been investigated to deliver exogenous insulin to the CNS. These alternative administrative routes can be utilized to increase the amount of CNS insulin and aid in overcoming CNS insulin resistance. This review focuses on the intravenous, intracerebroventricular, intranasal, ocular, and intrathecal routes of administration and compares the impact of insulin delivery.