This study was designed to examine the effect of exaggerated polyol-pathway flux on sciatic nerve content of polyols, myo-inositol, and water. Rats with streptozocin-induced diabetes of 3- and 12-wk duration and nondiabetic rats fed for 5 days on a diet containing 20% galactose were employed initially. All three conditions showed marked elevation of nerve polyol content, combined with fructose accumulation in the diabetic rats. Galactose-fed rats showed a significant (P < .01) increase in nerve water content of ∼30% (when expressed as water/unit dry wt tissue). Diabetic rats showed no change in nerve water. Both diabetic and galactose-fed rats showed a depletion of nerve free myo-inositol, although the extent of depletion was greater in the latter. All these changes were prevented or attenuated by the aldose reductase inhibitor Statil (IC1128436). When diabetic rats were fed a 20% galactose diet for 5 days, nerves of 3- but not 12-wk diabetic rats showed marked increases in water content. A more mild degree of galactosemia, induced by 5 or 21 days of feeding a diet containing 10% galactose to nondiabetic rats, provoked an increase in nerve water content associated with polyol levels of a similar order to those seen in diabetes. We do not know why polyol-pathway metabolites cause nerve hyperhydration in galactosemia but not in streptozocin-induced diabetes. Such differences urge caution in the use of galactose feeding to model the consequences of exaggerated polyol-pathway flux in nerve to face questions related to neuronal dysfunction in diabetes.

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