Lifestyle impacts on insulin transport at the blood‐brain barrier in mice

Abstract Background The blood‐brain barrier (BBB) is a regulatory interface, controlling the blood‐to‐brain transport of many substances, resulting in nutrient delivery to the central nervous system (CNS) and communication between the periphery and CNS. There are structural and functional changes within the BBB in Alzheimer’s disease, which may contribute to the detrimental effects occurring within the CNS. CNS insulin resistance is one of many detrimental features of Alzheimer’s disease. As the BBB is responsible for the delivery of insulin to the CNS, alterations in insulin BBB transport could be a cause of CNS insulin resistance. Indeed, various lifestyle factors are known to impact insulin BBB pharmacokinetics, including diet and exercise, which have also been shown to impact Alzheimer’s disease progression. Methods Utilizing sensitive radiotracer methods of substrate transport at the BBB in young male and female mice, we investigated the impact of exposure to a voluntary running wheel and what role CNS insulin resistance has on insulin BBB pharmacokinetics. Results Acute exercise increased insulin BBB transport and CNS insulin resistance decreased insulin brain uptake. Conclusion CNS insulin resistance decreases insulin BBB transport in mice, particularly in females. We found a lifestyle intervention, such as exercise, is able to enhance insulin BBB transport, which may be able to attenuate CNS insulin resistance. Future work is necessary to determine if exercise can reverse the insulin BBB transport deficiencies observed due to CNS insulin resistance.