ACETYL-L-CARNITINE DEFICIENCY AS A CAUSE OF ALTERED NERVE MYOINOSITOLCONTENT, NA,K-ATPASE ACTIVITY, AND MOTOR CONDUCTION-VELOCITY IN THE STREPTOZOTOCIN-DIABETIC RAT

Defective metabolism of long-chain fatty acids and/or their accumulati on in nerve may impair nerve function in diabetes by altering plasma o r mitochondrial membrane integrity and perturbing intracellular metabo lism and energy production. Carnitine and its acetylated derivatives s uch as acetyl-L-carnitine (ALC) promote fatty acid beta-oxidation in l iver and prevent motor nerve conduction velocity (MNCV) slowing in dia betic rats. Neither the presence nor the possible implications of puta tive ALC deficiency have been definitively established in diabetic ner ve. This study explored sciatic nerve ALC levels and the dose-dependen t effects of ALC replacement on sciatic nerve metabolites, Na,K-ATPase , and MNCV after 2 and 4 weeks of streptozotocin-induced diabetes (STZ -D) in the rat. ALC treatment that increased nerve ALC levels delayed (to 4 weeks) but did not prevent nerve myo-inositol (MI) depletion, bu t prevented MNCV slowing and decreased ouabain-sensitive (but not -ins ensitive) ATPase activity in a dose-dependent fashion. However, ouabai n-sensitive ATPase activity was also corrected by subtherapeutic doses of ALC that did not increase nerve ALC or affect MNCV. These data imp licate nerve ALC depletion in diabetes as a factor contributing to alt erations in nerve intermediary and energy metabolism and impulse condu ction in diabetes, but suggest that these alterations may be different ially affected by various degrees of ALC depletion. Copyright (C) 1996 by W.B. Saunders Company