Pathways for insulin access to the brain: the role of the microvascular endothelial cell.
Am J Physiol Heart Circ Physiol
; 311(5): H1132-H1138, 2016 11 01.
Article
em En
| MEDLINE
| ID: mdl-27591216
ABSTRACT
Insulin affects multiple important central nervous system (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 bISF, subarachnoid cerebrospinal fluid (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 wk 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Espaço Subaracnóideo
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Receptor de Insulina
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Barreira Hematoencefálica
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Líquido Cefalorraquidiano
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Líquido Extracelular
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Células Endoteliais
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Microvasos
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Hipoglicemiantes
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Insulina
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article