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Insulin transport across the blood–brain barrier can occur independently of the insulin receptor
Author(s) -
Rhea Elizabeth M.,
RaskMadsen Christian,
Banks William A.
Publication year - 2018
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp276149
Subject(s) - insulin , insulin receptor , blood–brain barrier , receptor , medicine , endocrinology , endothelial stem cell , biology , microbiology and biotechnology , central nervous system , insulin resistance , biochemistry , in vitro
Key points Insulin enters the brain from the blood via a saturable transport system. It is unclear how insulin is transported across the blood–brain barrier (BBB). Using two models of the signalling‐related insulin receptor loss or inhibition, we show insulin transport can occur in vivo without the signalling‐related insulin receptor. Insulin in the brain has multiple roles including acting as a metabolic regulator and improving memory. Understanding how insulin is transported across the BBB will aid in developing therapeutics to further increase CNS concentrations.Abstract A saturable system transports insulin from blood across the blood–brain barrier (BBB) and into the central nervous system. Whether or not the classic or signalling‐related insulin receptor plays a role in mediating this transport in vivo is controversial. Here, we employed kinetics methods that distinguish between transport across the brain endothelial cell and reversible luminal surface receptor binding. Using a previously established line of mice with endothelial‐specific loss of the signalling‐related insulin receptor (EndoIRKO) or inhibiting the insulin receptor with the selective antagonist S961, we show insulin transport across the BBB is maintained. Rates of insulin transport were similar in all groups and transport was still saturable. Unlike transport, binding of insulin to the brain endothelial cell was decreased with the loss or inhibition of the signalling‐related insulin receptor. These findings demonstrate that the signalling‐related insulin receptor is not required for insulin transport across the BBB.