Enhanced Insulin Binding to Blood-Brain Barrier In Vivo and to Brain Microvessels In Vitro in Newborn Rabbits

Insulin is a known growth factor in nonneural tissue, and recent studies have shown that there are insulin receptors throughout the adult and fetal central nervous system. Since insulin has only limited access to the adult brain, this study was undertaken to determine if insulin has increased availability to the newborn brain where it may act as a neonatal brain growth promotor. In vivo brain uptake of ¹²⁵I-Insulin after a single-pass carotid injection was measured in newborn, 3-wk-old and 11-wk-old (adult) rabbits. The brain uptake index (BUI) relative to a ³HOH reference was 22.0 ± 1.1% (mean ± SEM) for newborn, 12.8 ± 0.6% for 3-wk-old, and 6.5 ± 0.1% for adults. Specific ¹²⁵I-insulin binding to isolated cerebral microvessels was similarly increased in the newborn (60.6 ± 3.3 %/mg protein) compared with the 3-wk-old (23.8 ± 1.7) and adult animals (13.6 ± 1.9). Scatchard analysis revealed that the difference was due to an increase in receptor number with only minimal changes in the affinity. The increased availability of circulating insulin to the newborn brain was further corroborated by elevated CSF/serum and brain/serum insulin ratios in the newborn versus adult. These results suggest that insulin has increased access to the newborn brain where it may function as a growth factor.