Defects of axonal transport in experimental diabetes that are unrelated to the sorbitol pathway.

This study examined the effect of experimental diabetes on the anterograde and retrograde axonal transport of phosphofructokinase activity. Rats with streptozotocin-induced diabetes of 4 weeks duration showed phosphofructokinase activity accumulation deficits both proximal (53% and 65% in two separate experiments) and distal (80% and 70%) to 24-h sciatic nerve constrictions. There was no significant effect of diabetes on the phosphofructokinase activity per unit length in unconstricted sciatic nerve. Treatment of a group of diabetic rats with the aldose reductase inhibitor, sorbinil, profoundly reduced the concentrations of polyol pathway metabolites (sorbitol and fructose) in sciatic nerve. This effective inhibition of aldose reductase did not alter the accumulation deficits of phosphofructokinase activity on either side of sciatic nerve constrictions. We conclude that short-term experimental diabetes causes impaired axonal transport of phosphofructokinase activity by mechanisms unrelated to aldose reductase.