The rationale for these experiments is that administration of L-carnitine and/or short-chain acylcarnitines attenuates myocardial dysfunction 1) in hearts from diabetic animals (in which L-carnitine levels are decreased); 2) induced by ischemia-reperfusion in hearts from nondiabetic 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 diabetic peripheral neuropathy. The major findings in rats with streptozotocin-induced diabetes of 4–6 weeks duration were that 24-h urinary carnitine excretion was increased ∼ twofold and L-carnitine levels were decreased in plasma (46%) and sciatic nerve endoneurium (31%). These changes in carnitine levels/excretion were associated with decreased 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 permeation (increased 60%), and blood flow (increased 65%). Treatment with acetyl-L-carnitine normalized plasma and endoneurial L-carnitine levels and prevented all of these metabolic and functional changes except the increased blood flow, which was unaffected, and the reduction in DAG, which decreased another 40%. In conclusion, these observations 1) demonstrate a link between imbalances in carnitine metabolism and several metabolic and functional abnormalities associated with diabetic polyneuropathy and 2) indicate that decreased sciatic nerve endoneurial ATPase activity (ouabain-sensitive and insensitive) in this model of diabetes is associated with decreased DAG.
Neural Dysfunction and Metabolic Imbalances in Diabetic Rats: Prevention by Acetyl-L-Carnitine
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Yasuo Ido, Jane McHowat, Katherine C Chang, Edoardo Arrigoni-Martelli, Zaven Orfalian, Charles Kilo, Peter B Corr, Joseph R Williamson; Neural Dysfunction and Metabolic Imbalances in Diabetic Rats: Prevention by Acetyl-L-Carnitine. Diabetes 1 December 1994; 43 (12): 1469–1477. https://doi.org/10.2337/diab.43.12.1469
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