Action of Sorbinil in Diabetic Peripheral Nerve: Relationship of Polyol (Sorbitol) Pathway Inhibition to a myo-Inositol-mediated Defect in Sodium-Potassium ATPase Activity

Abstract

The small, but statistically significant, improvement in nerve conduction after treatment of diabetic patients with the aldose reductase inhibitor, sorbinil, suggests that increased polyol (sorbitol) pathway activity may contribute to diabetic nerve conduction slowing. Although classically viewed solely in terms of sorbitol-induced osmotic swelling, polyol pathway inhibition is now speculated to influence a concomitant myo-inositol-mediated alteration in nerve sodium-potassium ATPase activity in diabetic nerve. Therefore, we directly examined the effect of sorbinil treatment on sodium-potassium ATPase activity in crude homogenates of sciatic nerve from streptozotocin-diabetic and non-diabetic rats. We demonstrate that sorbinil treatment, which preserves normal nerve myo-inositol content, prevents the fall in nerve sodium-potassium ATPase activity that has been linked to conduction slowing in the diabetic rat.