What is it about?

Upon activation, neurons require extra energy and oxygen supply. This requirement is satisfied through a process dubbed “neurovascular coupling”, whereby active neurons obtain nutrients and oxygen on demand. Acting through astrocytes, an abundant type of non neuronal cell covering all the small vessels in the brain, insulin modulates the formation of new vessels and glucose capture. Insulin is a hormone involved in energy allocation throughout the body; acting at this unrecognized site it assures proper coupling between brain glucose needs and blood supply to this organ. Accordingly, disturbed insulin signaling onto astrocytes uncouples brain glucose uptake with brain blood flow due to excess oxidative stress at astrocyte mitochondria.

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Why is it important?

Altered insulin actions in brain have been related to various brain diseases, making the study of brain actions of this hormone a topic of medical interest. Under conditions of insufficient insulin input onto astrocytes, development of excess oxidative stress ensues and interferes with this novel function of insulin. Importantly, pharmacological amelioration of oxidative stress restores neurovascular coupling in mice with faulty insulin activity in astrocyes. As different brain maladies present altered glucose handling and/or brain blood flow, insulin receptors in astrocytes may constitute a new therapeutic target for these diseases.

Perspectives

While a role for astrocytes at the BBB has long been recognized, and insulin is known to modulate many brain activities, particularly those related to allocation of body energy, regulation of neurovascular coupling through insulin action onto this type of glial cells links angiogenic signaling from astrocytes with glucose and oxygen sensing by these cells, providing a feedback loop to blood flow homeostasis. These sensing abilities of astrocytes are under intense scrutiny, and their regulation by insulin merits a detailed analysis.

Ignacio Torres Aleman

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This page is a summary of: Insulin regulates neurovascular coupling through astrocytes, Proceedings of the National Academy of Sciences, July 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2204527119.
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