A new paradigm to understand and treat diabetic neuropathy
Hidmark A, Fleming T, Vittas S, Mendler M, Deshpande D, Groener JB, Mueller BP, Reeh P, Sauer S, Pham M, Muckenthaler MU, Bendszus M, Nawroth PP (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Publisher: Thieme Publishing / Georg Thieme Verlag
Book Volume: 122
Pages Range: 201-7
Journal Issue: 4
Abstract
The clinical symptoms of diabetic neuropathy (DN) manifest in a time dependent manner as a positive symptoms (i. e. pain, hypersensitivity, tingling, cramps, cold feet etc.) during its early stages and by a loss of function (i. e. loss of sensory perception, delayed wound healing etc.) predominating in the later stages. Elevated blood glucose alone cannot explain the development and progression of DN and the lowering of blood glucose is insufficient in preventing and/or reversing neuropathy in patients with type 2 diabetes. Recently it has been shown that the endogenous reactive metabolite methylglyoxal (MG) can contribute to the gain of function via post-translational modification in DN of neuronal ion channels involved in chemosensing and action potential generation in nociceptive nerve endings. Dicarbonyls, such as MG, that are elevated in diabetic patients, modify DNA as well as extra- and intracellular proteins, leading to the formation of advanced glycation endproducts (AGEs). Increased formation of AGEs leads to increased cellular stress, dysfunction and ultimately cell death. The interaction of AGE-modified proteins through cell surface receptors, such as RAGE, can lead to increased cellular activation and sustained inflammatory responses, which are the molecular hallmarks of the later, degenerative, stages of DN. The direct and indirect effects of dicarbonyls on nerves or neuronal microvascular network provides a unifying mechanism for the development and progression of DN. Targeting the accumulation of MG and/or prevention of RAGE interactions may therefore provide new, more effective, therapeutic approaches for the treatment of DN.
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Germany (DE)How to cite
APA:
Hidmark, A., Fleming, T., Vittas, S., Mendler, M., Deshpande, D., Groener, J.B.,... Nawroth, P.P. (2014). A new paradigm to understand and treat diabetic neuropathy. Experimental and Clinical Endocrinology and Diabetes, 122(4), 201-7. https://doi.org/10.1055/s-0034-1367023
MLA:
Hidmark, A., et al. "A new paradigm to understand and treat diabetic neuropathy." Experimental and Clinical Endocrinology and Diabetes 122.4 (2014): 201-7.
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