Inositol, Sorbitol and Diabetic Neuropathy

There is a reduced concentration of free inositol in sciatic nerve from rats made diabetic by injection of streptozotocin and in the same nerve obtained post-mortem from diabetic patients. Phosphatidylinositol concentration is reduced in sciatic nerves from acutely diabetic rats. Endoneurial preparations from less severely diabetic animals show decreased polyphosphoinositide. These changes may contribute to the neuropathy shown initially in these animals by reduced conduction velocity. Aldose reductase inhibition by the drug sorbinil lowers sorbitol concentrations in nerves from diabetic animals and at the same time restores inositol concentration to normal. Genetically diabetic mice show reduced sciatic nerve conduction velocity and lack of inositol, but have no additional sciatic nerve sorbitol. This suggests that lack of inositol is more important than excess sorbitol in the development of conduction defects. There is also evidence that phosphoinositides may have some connection with the sodium pump ATPase. This enzyme has been assayed in microsomal fractions from sciatic nerve. It appears less active in nerves from diabetic rats. The assay method used with homogenates of nerve by other workers has not been successful in our hands.