Summary
Intraneuronal accumulations of sorbitol and fructose have been postulated to predispose the nervous system to the cerebral edema associated with the treatment of diabetic ketoacidosis. In the present study, the enzymes of the pathway for the production of sorbitol and fructose, aldose reductase and sorbitol dehydrogenase, were localized histochemically in brain, spinal cord and sciatic nerve. Enzyme activity was limited to the choroidal epithelium, ependymal cells, and pia mater in normal, 2- and 10-week streptozotocin diabetic and vehicle-treated rats. Sorbitol dehydrogenase activity was located in blood vessels and perineurium of the sciatic nerve in these groups of rats. Comparison of diabetic and vehicle groups did not demonstrate any alteration in the activity of either enzyme in the central nervous system. However, there was a decrease in sorbitol dehydrogenase activity in the blood vessels in the sciatic nerve in 50% of the 10-week diabetic rats.
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Aloia J. F., Nilakantan S.: The cerebrospinal fluid in uncontrolled diabetes mellitus - Amer. J. med. Sci.266, 203, 1973.
Arieff A. I., Kleeman C. R.: Cerebral edema in diabetic comas. II. Effects of hyperosmolality, hyperglycemia and insulin in diabetic rabbits - J. clin. Endocr.38, 1057, 1974.
Clements R. S. Jr.,Blumenthal S. A., Morrison A. D., Winegrad A. I.: Increased cerebrospinal fluid pressure during treatment of diabetic ketosis - Lancet2, 671, 1971.
Clements R. S. Jr.,Prockop L. D., Winegrad A. I.: Acute cerebral oedema during treatment of hyperglycaemia - Lancet2, 384, 1968.
Clements R. S. Jr.,Weaver J. P., Winegrad A. I.: The distribution of polyol:NADP oxidoreductase in mammalian tissues - Biochem. biophys. Res. Commun.37, 347, 1969.
Dillon E. S., Riggs H. E., Dyer W. W.: Cerebral lesions in uncomplicated fatal diabetic acidosis - Amer. J. med. Sci.192, 360, 1936.
Dons R. F., Doughty C. C.: Isolation and characterization of aldose reductase from calf brain - Biochim. biophys. Acta (Amst.)452, 1, 1976.
Gabbay K. H., O'Sullivan J. B.: The sorbitol pathway. Enzyme localization and content in normal and diabetic nerve and cord - Diabetes17, 239, 1968.
Jakobsen J.: Peripheral nerves in early experimental diabetes. Expansion of the endoneural space as a cause of increased water content - Diabetologia14, 113, 1978.
Johnson A. B.: Histochemical demonstration of the soluble enzyme, ketose reductase (sorbitol dehydrogenase), by utilizing a new fixing solution - J. Histochem. Cytochem.13, 583, 1965.
Johnson A. B.: The use of phenazine methosulfate for improving the histochemical localization of ketose reductase (L-iditol:NAD oxidoreductase, or sorbitol dehydrogenase) - J. Histochem. Cytochem.15, 207, 1967.
Junod A., Lambert A. E., Stauffacher W., Renold A. E.: Diabetogenic action of streptozotocin: relationship of dose to metabolic response - J. clin. Invest.48, 2129, 1969.
Lillie R. D., Fullmer H. M.: Histopathologic technic and practical histochemistry - McGraw-Hill, New York, 1976; pp. 471–476.
Ludvigson M. A., Sorenson R. L.: Immunohistochemical localization of aldose reductase. I. Enzyme purification and antibody preparation-localization in peripheral nerve, artery and testis - Diabetes29, 438, 1980.
Moonsammy G. I., Stewart M. A.: Purification and properties of brain aldose reductase and L-hexonate dehydrogenase- J. Neurochem.14, 1187, 1967.
Prockop L. D.: Hyperglycemia, polyol accumulation, and increased intracranial pressure - Arch. Neurol. (Chic.)25, 126, 1971.
Regh J. E., Torack R. M.: Partial purification and characterization of sorbitol dehydrogenase from rat brain - J. Neurochem.28, 655, 1977.
Servo C., Pitkänen E.: Variation in polyol levels in cerebrospinal fluid and serum in diabetic patients - Diabetologia11, 575, 1975.
Stewart M. A., Sherman W. R., Kurien M. M.: Polyol accumulations in nervous tissue of rats with experimental diabetes and galactosemia - J. Neurochem.14, 1057, 1967.
Tabakoff B., Erwin V. G.: Purification and characterization of a reduced nicotinamide adenine dinucleotide phosphate-linked aldehyde reductase from brain. J. biol. Chem.245, 3263, 1970.
Thomas P. K., Lascelles R. G.: Schwann-cell abnormalities in diabetic neuropathy - Lancet1, 1355, 1965.
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Orosz, S.E., Townsend, S.F., Tornheim, P.A. et al. Localization of aldose reductase and sorbitol dehydrogenase in the nervous system of normal and diabetic rats. Acta diabet. lat 18, 373–381 (1981). https://doi.org/10.1007/BF02042822
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DOI: https://doi.org/10.1007/BF02042822