Askwith, Trevor (2010)
Ph.D. thesis, University of Birmingham.
It is estimated that 2.6 million people in the UK suffer from diabetes, 50% of whom suffer from diabetic neuropathy. Patients with diabetes have low levels of platelet and plasma taurine and in animal models taurine supplementation ameliorates neuropathic symptoms. The mechanisms behind Taurine depletion and taurine supplementation are not well understood. Schwann cells are highly vulnerable to hyperglycaemia-induced stress which plays a key role in the pathogenesis of diabetic neuropathy, however, the mechanisms behind these effects are not well understood. In these studies I have elucidated the effect of hyperglycaemia on taurine transport in isolated human Schwann cells and the mechanisms behind the beneficial effects of taurine supplementation. I demonstrated that high glucose reduces TauT expression in a dose-dependent manner and that high glucose inhibited the pro-oxidant increase in TauT expression and taurine uptake. This high glucose response was ablated by inhibition of aldose reductase, nitric oxide synthase as well as antioxidant treatment. Taurine supplementation reduced glucose-induced increases in oxidative stress, lipid peroxidation nitrosative stress and poly(ADP-ribosyl)ation and these effects were not accompanied by changes in antioxidant defence. Taurine also restored glucose-induced increases in iNOS and nNOS expression along with phospho-p38 MAPK abundance.
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