Central nervous system insulin signaling can influence the rate of insulin influx into brain

Fluids and Barriers of the CNS

卷:20

Research

Peter Thomas¹  Alice Babin¹  Riley Weaver¹  William A. Banks²  Elizabeth M. Rhea²  Cassidy Noonan³  Sarah Pemberton³  Van Nguyen⁴ 

[1] Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, 98108, Seattle, WA, USA;

[2] Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, 98108, Seattle, WA, USA;Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, 98195, Seattle, WA, USA;

[3] Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, 98108, Seattle, WA, USA;University of Washington, 98195, Seattle, WA, USA;

[4] School of Medicine, University of Washington, 98195, Seattle, WA, USA;

关键词: Blood-brain barrier;    Insulin receptor;    Insulin resistance;    Alzheimer’s disease;   

DOI  :  10.1186/s12987-023-00431-6

 received in 2022-12-09, accepted in 2023-04-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundInsulin transport across the blood-brain barrier (BBB) is a highly regulated, saturable process, known to be affected by many peripheral substrates including insulin itself and triglycerides. This is in contrast to insulin leakage into peripheral tissues. Whether the central nervous system (CNS) can control the rate of insulin uptake by brain remains to be determined. Insulin BBB interactions are impaired in Alzheimer’s disease (AD) and CNS insulin resistance is widely prevalent in AD. Therefore, if CNS insulin controls the rate of insulin transport across the BBB, then the defective transport of insulin seen in AD could be one manifestation of the resistance to CNS insulin observed in AD.MethodsWe investigated whether enhancing CNS insulin levels or induction of CNS insulin resistance using an inhibitor of the insulin receptor altered the blood-to-brain transport of radioactively labeled insulin in young, healthy mice.ResultsWe found that insulin injected directly into the brain decreased insulin transport across the BBB for whole brain and the olfactory bulb in male mice, whereas insulin receptor blockade decreased transport in female mice for whole brain and hypothalamus. Intranasal insulin, currently being investigated as a treatment in AD patients, decreased transport across the BBB of the hypothalamus.ConclusionsThese results suggest CNS insulin can control the rate of insulin brain uptake, connecting CNS insulin resistance to the rate of insulin transport across the BBB.

【 授权许可】

CC BY   
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

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