Tomlinson David R, Gardiner Natalie J
Faculty of Life Sciences, University of Manchester, Manchester, UK.
J Peripher Nerv Syst. 2008 Jun;13(2):112-21. doi: 10.1111/j.1529-8027.2008.00167.x.
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.
本综述探讨了葡萄糖在糖尿病神经病变病因学中的假定作用。过量的葡萄糖会产生多种继发性代谢异常，主要是氧化应激（通过多元醇途径和糖氧化作用）以及大分子的非酶糖基化。糖氧化作用也会促进后者。这些代谢偏差引发了与正常功能不相符的细胞反应。其中主要的是神经营养缺陷和丝裂原活化蛋白激酶（MAPK）的磷酸化。这些事件的下游是异常的离子通道功能和紊乱的基因表达，导致细胞表型发生变化。这直接导致神经传导紊乱，这是一种公认的早期临床症状，并且通过尚未明确的联系间接导致感觉丧失和轴突病。最近的研究还将MAPK激活与神经性疼痛的发展联系起来。
