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Diabetic neuropathies: components of etiology
Author(s) -
Tomlinson David R.,
Gardiner Natalie J.
Publication year - 2008
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1529-8027.2008.00167.x
Subject(s) - glycation , mapk/erk pathway , diabetic neuropathy , etiology , kinase , polyol pathway , diabetes mellitus , phenotype , neuroscience , phosphorylation , medicine , ion channel , neuropathic pain , neurotrophin , bioinformatics , biology , microbiology and biotechnology , endocrinology , gene , biochemistry , receptor , aldose reductase
This review examines the putative role of glucose in the etiology of diabetic neuropathies. Excessive glucose generates several secondary metabolic anomalies — principally oxidative stress (via both the polyol pathway and glucoxidation) and non‐enzymic glycation of macromolecules. The latter is also facilitated by glucoxidation. These metabolic deviations trigger cellular responses that are inappropriate to normal function. Principal among these are neurotrophic deficits and phosphorylation of mitogen‐activated protein kinases (MAPK). Downstream of these events are aberrant ion channel function and disordered gene expression, leading to changes in cellular phenotype. This leads directly to disordered nerve conduction, a recognised early clinical sign, and indirectly, via as yet undisclosed links, to sensory loss and axonopathy. Recent work also links MAPK activation to the development of neuropathic pain.