Diabetes, Vol 39, Issue 6 663-666, Copyright © 1990 by American Diabetes Association

ARTICLES

Coexistence of nerve conduction deficit with increased Na(+)-K(+)-ATPase activity in galactose-fed mice. Implications for polyol pathway and diabetic neuropathy

NA Calcutt, DR Tomlinson and S Biswas
Department of Pharmacology, St. Bartholomew's Hospital Medical College, London, United Kingdom.

We measured motor nerve conduction velocity (MNCV), Na(+)-K(+)-ATPase activity, polyol-pathway metabolites, and myo-inositol in sciatic nerves from control mice, galactose-fed (20% wt/wt diet) mice, and galactose-fed mice given the aldose reductase inhibitor ponalrestat (300-mg/kg diet). Treatments were maintained for 4 wk. Galactose feeding was associated with a 21.5% reduction in MNCV (P less than 0.001), which was almost completely prevented by ponalrestat. Galactose-fed mice showed an 81% increase in Na(+)-K(+)-ATPase (P less than 0.01), an effect completely prevented by aldose reductase inhibition. Treatment of a separate galactose-fed group with sorbinil (300 mg/kg diet) also attenuated the MNCV deficit and prevented the increased Na(+)-K(+)-ATPase activity associated with galactosemia. Accumulation of galactitol in the nerves of galactose-fed mice was prevented by aldose reductase inhibition, but there were no alterations in myo-inositol levels in the sciatic nerves of any group. These data show that exaggerated flux through the polyol pathway can cause an MNCV deficit that is unrelated to either myo-inositol levels or NA(+)-K(+)-ATPase activity.
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