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Taurine depletion and Schwann cell dysfunction in diabetic neuropathy

Askwith, Trevor (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

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.

Type of Work:Ph.D. thesis.
Supervisor(s):Stevens, Martin
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RC Internal medicine
Institution:University of Birmingham
ID Code:1179
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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