Insulin affects multiple important CNS functions including memory and appetite, yet the pathway(s) by which insulin reaches brain interstitial fluid (bISF) has not been clarified. Recent studies demonstrate that to reach brain interstitial fluid (bISF), subarachnoid CSF courses through the Virchow-Robin space (VRS) which sheaths penetrating pial vessels down to the capillary level. Whether insulin predominantly enters the VRS and bISF by local transport through the blood-brain barrier, or by being secreted into the CSF by the choroid plexus is unknown. We injected 125I-TyrA14-insulin or regular insulin intravenously and compared the rates of insulin reaching subarachnoid CSF with its plasma clearance by brain tissue samples (an index of microvascular endothelial cell binding/uptake/transport). The latter process was more than 40-fold more rapid. We then showed that selective insulin receptor blockade or 4 weeks of high-fat feeding each inhibited microvascular brain 125I-TyrA14-insulin clearance. We further confirmed that 125I-TyrA14-insulin was internalized by brain microvascular endothelial cells, indicating that the in vivo tissue association reflected cellular transport not simply microvascular tracer binding.
- Blood brain barrier
- Virchow-Robin space
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology