Delayed autoregulation of glucose transport in vascular endothelial cells.
OBJECTIVE
We aimed to characterise the development of autoregulation of glucose transport in vascular endothelial cells and its relationship to 12-lipoxygenase (12-LO) expression.


METHODS
Bovine aortic endothelial cells were exposed to 5.5 and 23.0 mmol/l glucose for up to 48 h. The rates of glucose transport, GLUT-1 and 12-LO expression and of 12-hydroxyeicosatetraenoic acid (12-HETE) production were determined.


RESULTS
We showed high glucose-dependent downregulation of glucose transport and transporter in vascular endothelial cells within 36-48 h. A similar time-dependent increase in the expression of 12-LO and the generation of its product 12-HETE was also observed. This downregulatory process was prevented when lipoxygenase activity was inhibited.


CONCLUSIONS
Vascular endothelial cells, which were previously thought to be "glucose-blind", do in fact downregulate GLUT-1 expression and the rate of glucose transport in response to extended exposure to high glucose concentrations. This slow development of glucose-induced downregulation in vascular endothelial cells is related to the slower basal rate of glucose transport in these cells and the slow induction of 12-LO. These data are interesting in view of current hypotheses that attribute vascular endothelial cell dysfunction in diabetes to the lack of a glucose-induced autoregulatory response.
Alpert
E
E
Department of Pharmacology, Hebrew University School of Medicine, P.O. Box 12272, Jerusalem, 91120, Israel.
Gruzman
A
A
Riahi
Y
Y
Blejter
R
R
Aharoni
P
P
Weisinger
G
G
Eckel
J
J
Kaiser
N
N
Sasson
S
S
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D051272:Glucose Transporter Type 1; D006027:Glycosides / Q000494:pharmacology; D006601:Hexoses / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011284:Pregnenolone / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D004791:Enzyme Inhibitors; D044950:Flavanones; D051272:Glucose Transporter Type 1; D006027:Glycosides; D006601:Hexoses; D016859:Lipoxygenase Inhibitors; D009004:Monosaccharide Transport Proteins; C081583:esculentin steroid; C006680:baicalein; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D011284:Pregnenolone; D001092:Arachidonate 12-Lipoxygenase; D005947:Glucose
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