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
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.