Effect of L-fucose on proliferation and myo-inositol metabolism in cultured cerebral microvessel and aortic endothelial cells.
Decreased myo-inositol metabolism possibly contributes to the development of diabetic complications including micro and macrovascular disease. Previous studies have shown that hyperglycemia may be partially responsible for this defect. We have found that L-fucose, a monosaccharide present in low concentrations in normal circulation and found to be elevated in diabetes, causes defects in cultured endothelial cells, including alterations in myo-inositol metabolism and proliferation. Murine cerebral microvessel and bovine aortic endothelial cells take up L-fucose from the medium in a time and concentration-dependent manner. Both acute and chronic exposure of these cultured endothelial cells to media containing L-fucose at concentrations that may exist in diabetic sera cause a significant decrease in the accumulation of myo-inositol and its incorporation into inositol phospholipids. There is a concomitant decrease in the intracellular levels of myo-inositol. Kinetic analysis of the effect of L-fucose on myo-inositol uptake suggests that L-fucose competitively inhibits the transport of myo-inositol, exhibiting a Ki in the range of 1.6-4.1 mM for both cell types. Endothelial cells exposed to L-fucose concentrations of 0.5-20 mM exhibit depressed rates of proliferation in a concentration-dependent fashion. Furthermore, L-fucose causes a concentration-dependent decrease in synthesis of proteoglycan by cultured cerebral microvessel endothelial cells as measured by incorporation of 35S; however, this effect is not observed in the aortic endothelia. These data suggest that L-fucose at concentrations that may exist in diabetic sera may impair myo-inositol metabolism and proliferation of the vascular endothelium.
Stefani
M R
MR
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, Iowa.
Dunlap
J A
JA
Yorek
M A
MA
D000596:Amino Acids / Q000493:pharmacokinetics; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000098:blood supply*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005643:Fucose / Q000494:pharmacology*; D005947:Glucose / Q000493:pharmacokinetics; D007294:Inositol / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008833:Microcirculation; D011509:Proteoglycans / Q000096:biosynthesis
D000596:Amino Acids; D011509:Proteoglycans; D005643:Fucose; D007294:Inositol; D005947:Glucose