R. Pop-busui et al., Depletion of taurine in experimental diabetic neuropathy: Implications fornerve metabolic, vascular, and functional deficits, EXP NEUROL, 168(2), 2001, pp. 259-272
In diabetes, increased oxidative stress, disruption of signal transduction
pathways, and endothelial dysfunction have been critically implicated in th
e pathogenesis of experimental diabetic neuropathy (EDN). The development o
f nerve conduction slowing in diabetes is accompanied by depletion of the p
-amino acid taurine, Since taurine functions as an antioxidant, calcium mod
ulator, and vasodilator, taurine depletion may provide a pathogenetic link
between nerve metabolic, vascular, and functional deficits complicating dia
betes, The mechanism(s) of nerve taurine depletion, the localization of cri
tical taurine deficits, and its pathophysiological significance in EDN are
however unknown. This study explored the pathophysiological effects of sele
ctive nerve taurine replacement in streptozotocin-diabetic (STZ-D) rats. A
polyclonal human taurine transporter (TT) antibody was also generated in or
der to determine potential loci of critical taurine depletion. Two weeks of
STZ-D reduced sciatic motor nerve conduction velocity (NCV) by 23% (P < 0,
01), decreased composite nerve blood flow by 38% (P < 0,01), and reduced ne
rve taurine content by 29% (P < 0,05). In STZ-D rats, a 1% taurine diet cor
rected nerve taurine depletion, prevented motor NCV slowing, and partially
attenuated composite nerve blood flow deficits. After 6 weeks of STZ-D, a 1
% taurine diet ameliorated motor NCV slowing and endoneurial nutritive bloo
d flow deficits, prevented digital sensory NCV slowing, and reduced ouabain
-sensitive nerve (Na,K)-ATPase activity. Immunohistochemical studies locali
zed taurine and the TT to the vascular endothelium and Schwann cells of the
sciatic nerve. In conclusion, taurine depletion in the vascular endotheliu
m and Schwann cells of the sciatic nerve may contribute to the neurovascula
r and metabolic deficits in EDN, <(c)> 2001 Academic Press.