OSMOTICALLY-INDUCED NERVE TAURINE DEPLETION AND THE COMPATIBLE OSMOLYTE HYPOTHESIS IN EXPERIMENTAL DIABETIC NEUROPATHY IN THE RAT

Citation
Mj. Stevens et al., OSMOTICALLY-INDUCED NERVE TAURINE DEPLETION AND THE COMPATIBLE OSMOLYTE HYPOTHESIS IN EXPERIMENTAL DIABETIC NEUROPATHY IN THE RAT, Diabetologia, 36(7), 1993, pp. 608-614
Citations number
54
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Journal title
ISSN journal
0012186X
Volume
36
Issue
7
Year of publication
1993
Pages
608 - 614
Database
ISI
SICI code
0012-186X(1993)36:7<608:ONTDAT>2.0.ZU;2-Q
Abstract
Diabetic neuropathy results from progressive nerve fibre damage with b lunted nerve regeneration and repair and may be complicated by nerve h yperexcitability resulting in pain. The naturally occurring amino acid taurine functions as an osmolyte, inhibitory neurotransmitter, and mo dulator of pain perception. It is also known to have neurotrophic acti ons. The compatible osmolyte hypothesis proposes that levels of intrac ellular organic osmolytes including taurine and myo-inositol, respond co-ordinately in response to changes in intracellular sorbitol or exte rnal osmolality to maintain the intracellular milieu. We hypothesize t hat glucose-induced sorbitol accumulation in diabetes mellitus will re sult in taurine depletion in peripheral nerve which may potentially im pair nerve regeneration and precipitate neuronal hyperexcitability and pain. This study explored the relationships of taurine, myo-inositol and sorbitol in the rat nerve and their effects on nerve conduction ve locity. Osmolyte levels and nerve conduction velocity were determined in sciatic nerve from non-diabetic and streptozotocin-induced diabetic rats, with or without dietary taurine or myo-inositol supplementation . Taurine levels decreased by 31 % (p < 0.01) and myo-inositol decreas ed by 37 % (p < 0.05) in diabetic nerve as sorbitol accumulated. Tauri ne supplementation of diabetic animals did not affect nerve conduction velocity but further reduced nerve myo-inositol levels. Prevention of sorbitol accumulation with the aldose reductase inhibitor sorbinil in creased nerve taurine levels by 22 % (p < 0.05) when compared with unt reated diabetic animals. Thus, we have demonstrated an interdependence of organic osmolytes within the nerve. Abnormal accumulation of one o smolyte results in reciprocal depletion of others. Diabetic neuropathy may be an example of maladaptive osmoregulation, nerve damage and ins tability being aggravated by taurine depletion.