Abstract:

Insulin and the blood-brain barrier (BBB) interact in at least two distinct ways that are related to cognitive impairment.  Insulin plays important roles in cognition, neurogenesis, and CNS mediated metabolic regulation. Yet nearly all of the insulin is produced by the pancreas and dependent on transport by the BBB.  Evidence suggests that impaired insulin transport at the BBB and resistance within the brain occur in Alzheimer’s disease.  Additionally, the BBB deteriorates with the hyperglycemia of diabetes.  This talk will briefly explore these two mechanisms. After a general overview of BBB and insulin transport, mechanisms by which hyperglycemia through oxidative stress results in pericyte death and BBB disruption will be discussed.  I will then discuss CNS insulin resistance and therapeutic approaches to overcoming it.