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Blood—Brain Barrier Glucose Transporter
Author(s) -
Simpson Ian A.,
Appel Nathan M.,
Hokari Mitsuhiko,
Oki Jun,
Holman Geoffrey D.,
Maher Fran,
KoehlerStec Ellen M.,
Vannucci Susan J.,
Smith Quentin R.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720238.x
Subject(s) - glut1 , glucose transporter , blood–brain barrier , glut3 , medicine , glucose transporter type 1 , endocrinology , hypoglycemia , microvessel , glucose uptake , chemistry , insulin , glucose homeostasis , biology , central nervous system , angiogenesis , insulin resistance
: The transport of glucose across the blood‐brain barrier(BBB) is mediated by the high molecular mass (55‐kDa) isoform of the GLUT1glucose transporter protein. In this study we have utilized the tritiated,impermeant photolabel2‐ N ‐[4‐(1‐azi‐2,2,2‐trifluoroethyl)[2‐ 3 H]propyl]‐1,3‐bis( d ‐mannose‐4‐yloxy)‐2‐propylamineto develop a technique to specifically measure the concentration of GLUT1glucose transporters on the luminal surface of the endothelial cells of theBBB. We have combined this methodology with measurements of BBB glucosetransport and immunoblot analysis of isolated brain microvessels for labeledluminal GLUT1 and total GLUT1 to reevaluate the effects of chronichypoglycemia and diabetic hyperglycemia on transendothelial glucose transportin the rat. Hypoglycemia was induced with continuous‐release insulin pellets(6 U/day) for a 12‐ to 14‐day duration ; diabetes was induced bystreptozotocin (65 mg/kg i.p.) for a 14‐ to 21‐day duration. Hypoglycemiaresulted in 25‐45% increases in regional BBB permeability‐surface area( PA ) values for d ‐[ 14 C]glucose uptake, whenmeasured at identical glucose concentration using the in situ brain perfusiontechnique. Similarily, there was a 23 ± 4% increase in total GLUT1/mgof microvessel protein and a 52 ± 13% increase in luminal GLUT1 inhypoglycemic animals, suggesting that both increased GLUT1 synthesis and aredistribution to favor luminal transporters account for the enhanced uptake.A corresponding (twofold) increase in cortical GLUT1 mRNA was observed by insitu hybridization. In contrast, no significant changes were observed inregional brain glucose uptake PA , total microvessel 55‐kDa GLUT1, or luminal GLUT1 concentrations in hyperglycemic rats. There was, however, a 30‐40% increase in total cortical GLUT1 mRNA expression, with a 96% increase in the microvessels. Neither condition altered the levels of GLUT3 mRNA or protein expression. These results show that hypoglycemia, but not hyperglycemia, alters glucose transport activity at the BBB and that these changes in transport activity result from both an overall increase in total BBB GLUT1 and an increased transporter concentration at the luminal surface.