NEURAL DYSFUNCTION AND METABOLIC IMBALANCES IN DIABETIC RATS PREVENTION BY ACETYL-L-CARNITINE

The rationale for these experiments is that administration of L-carnit ine and/or short-chain acylcarnitines attenuates myocardial dysfunctio n 1) in hearts from diabetic animals Cin which L-carnitine levels are decreased); 2) induced by ischemia-reperfusion in hearts from nondiabe tic animals; and 3) in nondiabetic humans with ischemic heart disease. The objective of these studies was to investigate whether imbalances in carnitine metabolism play a role in the pathogenesis of diabe tic p eripheral neuropathy. The major findings in rats with streptozotocin-i nduced diabetes of 4-6 weeks duration were that 24-h urinary carnitine excretion was increased approximately twofold and L-carnitine levels were decreased in plasma (46%) and sciatic nerve endoneurium (31%). Th ese changes in carnitine levels/excretion were associated with decreas ed caudal nerve conduction velocity (10-15%) and sciatic nerve changes in Na+-K+ ATPase activity (decreased 50%), Mg2+-ATPase (decreased 65% ), 1,2-diacyl-sn-glycerol (DAG) (decreased 40%), vascular albumin perm eation (increased 60%), and blood flow (increased 65%). Treatment with acetyl-L-carnitine normalized plasma and endoneurial L-carnitine leve ls and prevented all of these metabolic and functional changes except the increased blood flow, which was unaffected, and the reduction in D AG, which decreased another 40%. In conclusion, these observations 1) demonstrate a link between imbalances in carnitine metabolism and seve ral metabolic and functional abnormalities associated with diabetic po lyneuropathy and 2) indicate that decreased sciatic nerve endoneurial ATPase activity (ouabain-sensitive and insensitive) in this model of d iabetes is associated with decreased DAG.