A quantitative overview of glucose dynamics in the gliovascular unit

L. Felipe Barros*, Carla X. Bittner, Anitsi Loaiza, Omar H. Porras

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículo de revisiónrevisión exhaustiva

107 Citas (Scopus)

Resumen

While glucose is constantly being "pulled" into the brain by hexokinase, its flux across the blood brain barrier (BBB) is allowed by facilitative carriers of the GLUT family. Starting from the microscopic properties of GLUT carriers, and within the constraints imposed by the available experimental data, chiefly NMR spectroscopy, we have generated a numerical model that reveals several hidden features of glucose transport and metabolism in the brain. The half-saturation constant of glucose uptake into the brain (Kt) is close to 8 mM. GLUT carriers at the BBB are symmetric, show accelerated-exchange, and a Km of zero-trans flux (Kzt) close to 5 mM, determining a ratio of 3.6 between maximum transport rate and net glucose flux (Tmax/ CMRglc). In spite of the low transporter occupancy, the model shows that for a stimulated hexokinase to pull more glucose into the brain, the number or activity of GLUT carriers must also increase, particularly at the BBB. The endothelium is therefore predicted to be a key modulated element for the fast control of energy metabolism. In addition, the simulations help to explain why mild hypoglycemia may be asymptomatic and reveal that [glucose]brain (as measured by NMR) should be much more sensitive than glucose flux (as measured by PET) as an indicator of GLUT1 deficiency. In summary, available data from various sources has been integrated in a predictive model based on the microscopic properties of GLUT carriers.

Idioma originalInglés
Páginas (desde-hasta)1222-1237
Número de páginas16
PublicaciónGLIA
Volumen55
N.º12
DOI
EstadoPublicada - 2007
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Neurología
  • Neurociencia celular y molecular

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