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Hirohito Sone, Baljit K. Deo, Arno K. Kumagai; Enhancement of Glucose Transport by Vascular Endothelial Growth Factor in Retinal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2000;41(7):1876-1884.
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purpose. To investigate effects of vascular endothelial growth factor (VEGF) on
glucose transport and GLUT1 glucose transporter expression in primary
bovine retinal endothelial cell (BREC) cultures.
methods. Glucose transport in control and VEGF-treated BREC cultures was
determined by measurement of[ 14C]-3-O-methylglucose (3MG) uptake.
GLUT1 protein and mRNA was determined by Western and Northern blot
analyses, respectively. Protein kinase C (PKC) activity was measured in
control and VEGF-treated cultures, and glucose transport was determined
with and without prior PKC depletion and PKC inhibition.
results. Dose-dependent increases in 3MG uptake were seen in the VEGF-treated
cultures, with an increase of 69% after a 24-hour exposure to 50 ng/ml
VEGF (P < 0.001). Total cellular GLUT1 mRNA or
protein, however, was unchanged. Western blot analysis of plasma
membrane fractions revealed a 75% increase in plasma membrane GLUT1 in
VEGF-treated cultures (P = 0.02), suggesting that
the VEGF-stimulated increase in glucose transport was due to a
translocation of GLUT1 to the cell membrane. VEGF stimulated a 90%
increase in PKC activity in membrane fractions from cultures treated
with VEGF, and VEGF-stimulated enhancement of glucose transport was
abolished by cellular PKC depletion and by general and PKC β
conclusions. The present study demonstrates VEGF-mediated enhancement of retinal
endothelial cell glucose transport and suggests that this increase is
due to PKC β–mediated translocation of cytosolic GLUT1 to the plasma
membrane surface. Upregulation of retinal endothelial cell glucose
transport by various factors associated with the development of
retinopathy may be responsible for the metabolic derangements observed
in the diabetic inner blood–retinal barrier in
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