Osmotic Stress Induces Aldose Reductase in Glomerular Endothelial Cells
Compelling evidence from animal studies (Robison et al, 1989, Notvest and Inserra, 1987; McCaleb et al, 1988, Kador et al 1988; c.f. Dvornik, 1987) and recent results from human clinical trials (Sima et al, 1988; Boulton, 1989) have implicated aldose reductase (AR), the first enzyme in the polyol pathway, in the initiation of a number of the long-term complications of diabetes. These complications develop in tissues where glucose uptake is independent of insulin. In these tissues during diabetes-induced hyperglycemia there is an intense flux of glucose through the polyol pathway which initiates a cascade of biochemical alterations that slowly progress to cell dysfunction and structural damage. While the role of AR in the pathogenesis of diabetic complications is well documented, its physiologic role, if any, under normal glycemic conditions is still unknown.
KeywordsAldose Reductase Polyol Pathway Aldose Reductase Inhibitor Slot Blot Glomerular Endothelial Cell
Unable to display preview. Download preview PDF.
- Boulton, A.J.M., Atiea, J., De Leeuw, LH., Lemkes, H., MacLeod, A.F., acRury, S., Scarpello, J.H.B., Somers, G., Tattersall, R.B. and Van Der Veen, E.A., 1989, The efficacy and safety of the aldose reductase inhibitor tolrestat in the treatment of chronic sensorimotor diabetic neuropathy. Diabetologia, 32:469A.Google Scholar
- Carper, D., Nishimura, C., Shinohara, T., Dietzchold, B., Wistow, G.,Google Scholar
- Chirgwin, J.M., Prybyla, A.E., MacDonald, R.J. and Rutter, W.J., 1986, Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochem., 18:5294.Google Scholar
- Davis, L.G., Dibner, M.D. and Battey, J.F., 1986, Formaldehyde gel for electrophoretic separation of RNA and Northern blot, in: Basic Methods in Molecular Biology. Elsevier Science Publ. Co., Inc., New York, 143–146.Google Scholar
- Dvornik, D., 1987, Aldose Reductase Inhibition: an Approach to the prevention of diabetic Complications. McGraw Hill, New York, pp368.Google Scholar
- Garcia-Perez, A., Martin, B., Murphy, H.R., Uchida, S., Murer, H., Cowley, B.D., Handler, J.S. and Burg, M.B., 1989, Molecular cloning of cDNA coding for kidney aldose reductase. J. Bio. Chem., 264:16815.Google Scholar
- McCaleb, M.L., Sredy, J. Milien, J., Ackerman, D.M., Dvornik, D., 1988, Prevention of urinary albumin excretion in 6 month streptozocin-diabetic rats with the aldose reductase inhibitor tolrestat. J. Diab. Compl., 2:16.Google Scholar
- Robison, W.G., Jr., Nagata, M., Laver, N., Hohman, T.C and Kinoshita, J.H., 1989, Diabetic-like retinopathy in rats prevented with an aldose reductase inhibitor. Invest. Ophthalmol. Vis. Sei., 30:2285.Google Scholar
- Sima, A.A.F., Bril, V., Nathaniel, V., McEwen, T.A.J., Brown, M.B., Lattimer, S.A., and Greene, D.A., 1988, Regeneration and repair of myelinated fibers in sural-nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil. New Engl. J. Med., 319:548.PubMedCrossRefGoogle Scholar
- Wirthensohn, G., Lefrank, S., Schmolke, M. and Guder, W.G., 1989, Regulation of organic osmolyte concentrations in tubules from rat renal inner medulla. American J. Physiol., 256:F128.Google Scholar
- Yancey, P.H., Burg, M.B. and Bagnasco, S.M., 1990, Effects of NaCl, lucose, and aldose reductase inhibitors on cloning efficiency of enal medullary cells. American J. Physiol., 258:C156.Google Scholar