Evidence for an alternative insulin transporter at the blood-brain barrier

Abstract

Accumulating evidence suggests there is an alternative insulin transporter besides the insulin receptor at the blood-brain barrier (BBB), responsible for shuttling insulin from the circulation into the brain. In this review, we summarize key features of the BBB and what makes it unique compared to other capillary beds; summarize what we know about insulin BBB transport; provide an extensive list of diseases, physiological states, and serum factors tested in modifying insulin BBB transport; and lastly, highlight potential alternative transport systems that may be involved in or have already been tested in mediating insulin BBB transport. Identifying the transport system for insulin at the BBB would aide in controlling central nervous system (CNS) insulin levels in multiple diseases and conditions including Alzheimer’s disease (AD) and obesity, where availability of insulin to the CNS is limited

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“…These transporters facilitate the movement of substances through the endothelial cells, ensuring their controlled and specific passage. Large molecules, like insulin, can cross the BBB through receptor‐mediated transcytosis triggering internalization and transport of the complex across the cells 46 . Certain peptides and proteins, characterized by positively charged residues, can cross the BBB by adsorptive transcytosis.…”

“…Large molecules, like insulin, can cross the BBB through receptor‐mediated transcytosis triggering internalization and transport of the complex across the cells. 46 Certain peptides and proteins, characterized by positively charged residues, can cross the BBB by adsorptive transcytosis. They interact with negatively charged components of the endothelial cell membrane, facilitating their transcellular transport.…”