Elsevier

Brain Research

Volume 420, Issue 1, 8 September 1987, Pages 32-38
Brain Research

Blood-brain barrier transcytosis of insulin in developing rabbits

https://doi.org/10.1016/0006-8993(87)90236-8Get rights and content

Abstract

Previous studies with isolated brain microvessels have suggested that blood insulin is selectively transported through the brain capillary, i.e. the blood-brain barrier (BBB), by receptor-mediated transcytosis. The purpose of the present study is to demonstrate in vivo the uptake of circulating125I-insulin by brain using thaw-mount autoradiography. However, metabolism of systemic125I-insulin to125I-tyrosine would allow for brain uptake of125I-tyrosine and this would preclude interpretation of the autoradiogram. Therefore, the present studies were performed in developing rabbits, since plasma protein degradation of peptides is greatly reduced in developing animals.125I-insulin was infused via the carotid artery at a rate of 0.25ml/min for 1,5, or 10 min, and the mean brain uptake, relative to a [3H]albumin reference, was 99.3±5.5%, 110.1±4.3%, and 143.6±7.9%, respectively. This uptake was saturable by simultaneously infusing unlabeled insulin. Thaw-mount autoradiography of rabbit brain after a 10-min infusion of125I-insulin revealed silver grains in the pericapillary space and well within the brain parenchyma. HPLC analysis of acid-ethanol extracts of rabbit blood after a 10-min infusion showed virtually all of the125I-radioactivity co-migrated with a known insulin standard on a reverse-phase column, indicating minimal degradation of infused125I-insulin. HPLC analysis of brain radioactivity showed the major peak co-migrated with125I-insulin and this peak was precipitated by an anti-insulin antiserum. The correlation of the transport data, the autoradiography, and the HPLC analysis support the model that brain insulin originates from blood via receptor-mediated transport of the peptide at the BBB.

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