Insulin detemir is not transported across the blood–brain barrier

Insulin detemir has a different profile of action on the central nervous system (CNS) than human insulin. It has been hypothesized that this is caused by an altered ability of insulin detemir to cross the blood–brain barrier (BBB). Here, we measured the permeability of the BBB to insulin detemir. We labeled insulin detemir with radioactive iodine (I-Det) and examined its ability to cross the BBB of the mouse. Permeation was assessed after intravenous injection and by brain perfusion in the presence or absence of excess insulin detemir. The ability of insulin detemir to inhibit human insulin transport across the BBB was also assessed. I-Det did not cross the BBB either after intravenous injection or when studied by brain perfusion, a method which removes or reduces the influence of circulating proteins. Unlabeled detemir was about 10 times less potent than human insulin at inhibiting the transport of radioactive human insulin across the BBB. The altered CNS profile of insulin detemir may be caused by its poor access to CNS receptors and by a block of human insulin from crossing the BBB.

Research highlights▶ Insulin detemir does not cross the blood–brain barrier. ▶ Insulin detemir inhibits the transport of insulin across the blood–brain barrier. ▶ The effects of insulin detemir are likely mediated through indirect mechanisms.