Summary
The regulation of GLUT-3 and aldose reductase mRNA in retinal endothelial cells and retinal pericytes was studied in response to variations in the extracellular concentration of hexoses. In physiological concentrations of glucose (5 mmol/l), an increase in the level of GLUT-3 mRNA was observed in cultured cells compared to the level of mRNA found in the absence of glucose. In contrast, there was little change in the level of GLUT-3 mRNA when the cells were cultured in the presence of 5 mmol/l galactose. In high concentrations of glucose, there was a decline in GLUT-3 mRNA indicating that the GLUT-3 mRNA is regulated by the extracellular concentration of glucose. In contrast, at both 5 mmol/l and 25 mmol/l glucose, the level of aldose reductase mRNA was increased. Furthermore, there were differences in the magnitude of the increase of aldose reductase mRNA between bovine retinal pericytes and bovine retinal endothelial cells with a greater increase being observed in the pericytes. We propose that this demonstration of a facultative glucose transporter system within retinal cells, and in particular the specific response to different hexoses and the known distinct kinetic parameters of the transporter system in specific cell types, highlights the heterogeneity of hexose transport mechanisms in retinal cells. Thus, hypergalactosaemia as a model system for the study of diabetic retinopathy should be used with caution.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Herman WH, Teutsch SM, Sepe SJ, Sinnock P, Klein R (1983) An approach to the prevention of blindness in diabetes. Diabetes Care 6: 608–613
Klein R, Klein BEK, Moss SE, Davis MD, DeMeyts DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy. II Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. III Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 years or more. Arch Ophthalmol 102: 520–532
Gould G, Bell GI (1990) Facilitative glucose transporters: an expanding family. Trend Biochem Sci 15: 18–23
Gould GW, Brant AM, Kahn BB, Shepherd PR, McCoid SC, Gibbs EM (1992) Expression of the brain type glucose transporter is restricted to brain and neuronal cells in mice. Diabetologia 35: 304–309
Nagamatsu S, Kornhauser JM, Burant CF, Seino S, Mayo KE, Bell GI (1992) Glucose transporter expression in Brain. J Biol Chem 267: 467–472
Gerhart DZ, Broderius MA, Borson ND, Drewes LR (1992) Neurons and microvessels express the brain glucose transporter protein GLUT-3. Proc Natl Acad Sci USA 89: 733–737
Kinoshita JH, Fukushi S, Kador P, Merola LO (1979) Aldose reductase in diabetic complications of the eye. Metabolism 28: 462–469
Akagi Y, Kador PF, Kuwabara T, Kinoshita JH (1983) Aldose reductase localization in human retinal mural cells. Invest Ophthalmol Vis Sci 24: 1516–1519
Frank RN, Keirn RJ, Kennedy A, Frank KW (1983) Galactoseinduced retinal capillary basement membrane thickening: prevention by sorbinil. Invest Ophthalmol Vis Sci 24: 1519–1524
Lightman S, Rechthand E, Terubayashi H, Palestine A, Rapoport S, Kador P (1987) Permeability changes in blood-retinal barrier of galactosemic rats are prevented by aldose reductase inhibitors. Diabetes 36: 1271–1275
Lightman S, Bondy C, Lightman S, Kador P (1990) Aldose reductase messenger RNA in the lens epithelium in vivo: effects of diabetes mellitus and galactosemia. Clin Sci 79: 599–603
Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159
Gould GW, Thomas HM, Jess TJ, Bell GI (1991) Expression of human glucose transporters in Xenopus oocytes: kinetic characterization and substrate specificities of the erythrocyte, liver and brain isoforms. Biochemistry 30: 5139–5145
Petrash N, Favello AD (1989) Isolation and characterization of cDNA clones encoding aldose reductase. Curr Eye Res 8: 1021–1027
Sognier MA, Neft RE, Roe AL, Eberle RL, Belli JA (1991) Dotblot hybridization: quantitative analysis with direct beta counting. Biotechniques 11: 520–525
Yano H, Seino Y, Inagaki N et al. (1991) Tissue distribution and species difference of the brain type glucose transporter (GLUT-3). Biochem Biophys Res Comm 174: 470–477
Bondy CA, Lightman SL (1989) Development and physiological regulation of aldose reductase mRNA expression in renal medulla. Mol Endocrinol 3: 1409–1416
Li W, Chan LW, Khatami M, Rockey JH (1985) Characterization of glucose transport by bovine retinal capillary pericytes in culture. Exp Eye Res 41: 191–199
Inagaki N, Yasuda K, Inoue G et al. (1992) Glucose as a regulator of glucose transport activity and glucose transporter mRNA in hamster β-cell line. Diabetes 41: 592–597
Walker PS, Donovan JA, Van Ness BG et al. (1988) Glucose dependent regulation of glucose transport activity, protein and mRNA in primary cultures of rat brain glial cells. J Biol Chem 263: 15594–15600
Choi TB, Boado RJ, Pardridge WM (1989) Blood-brain barrier glucose transporter mRNA is increased in experimental diabetes. Biochem Biophys Res Comm 164: 375–380
Engerman RL, Kern TS (1984) Experimental galactosemia produces diabetic-like retinopathy. Diabetes 33: 97–100
Sato S, Takahashi Y, Wyman M, Kador PF (1991) Progression of sugar cataract in the dog. Invest Ophthalmol Vis Sci 32: 1925–1931
Vaca-Pacheco G, Medina C, Garcia-Cruz D et al. (1990) Identification of inborn metabolic errors of galactose in patients with cataracts. Arch Invest Med 21: 127–132
Gabbay KH (1973) The sorbitol pathway and the complications of diabetes. N Engl J Med 288: 831–836
Vinores SA, Campochiaro PA, Williams EH, May EE, Green WR (1988) Aldose reductase expression in human diabetic retina and retinal pigment epithelium. Diabetes 37: 1658–1664
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Knott, R.M., Robertson, M. & Forrester, J.V. Regulation of glucose transporter (GLUT 3) and aldose reductase mRNA in bovine retinal endothelial cells and retinal pericytes in high glucose and high galactose culture. Diabetologia 36, 808–812 (1993). https://doi.org/10.1007/BF00400354
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00400354