Shimatani Yoshimitsu, Nodera Hiroyuki, Osaki Yusuke, Banzrai Chimeglkham, Takayasu Kazuhiro, Endo Sachiko, Shibuta Yoshiko, Kaji Ryuji
Department of Neurology, Tokushima University, Tokushima, Japan.
Department of Neurology, Tokushima University, Tokushima, Japan.
Clin Neurophysiol. 2015 Nov;126(11):2226-32. doi: 10.1016/j.clinph.2015.02.058. Epub 2015 Mar 14.
To describe functional changes of axonal ion channels by a metabolic derivative of glucose, methylglyoxal (MGO), and its potential contribution to diabetic neuropathy.
(1) In wild-type male mice, multiple excitability measurements of sensory nerves were performed at baseline and 1week after serial administration of MGO (50mg/kg). (2) Excitability testing in patients with diabetic neuropathy (N=17) and healthy controls (N=12) were also conducted, and data were interpreted using mathematical modeling.
In the animal study, there was a decrease in threshold changes by long hyperpolarization and in superexcitability after administration of MGO. In the preliminary human study, the threshold changes by long hyperpolarizing current were decreased in patients with diabetes. Mathematical modeling showed increased hyperpolarization-activated cation current (Ih) in the MGO-treated mice and in patients with diabetes.
Ih was upregulated after MGO administration in normal mice.
MGO is associated with abnormal axonal excitability. Hyperexcitability in diabetic polyneuropathy may, at least in part, be caused by dysfunctional axonal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. A future study with a large sample size of the diabetic patients would clarify this hypothesis.
描述葡萄糖的代谢衍生物甲基乙二醛（MGO）对轴突离子通道的功能改变及其对糖尿病神经病变的潜在影响。
（1）对野生型雄性小鼠，在基线状态及连续给予MGO（50mg/kg）1周后，对感觉神经进行多次兴奋性测量。（2）对糖尿病神经病变患者（N = 17）和健康对照者（N = 12）进行兴奋性测试，并使用数学模型解释数据。
在动物研究中，给予MGO后，长时间超极化引起的阈值变化及超兴奋性均降低。在初步的人体研究中，糖尿病患者长时间超极化电流引起的阈值变化降低。数学模型显示，MGO处理的小鼠及糖尿病患者的超极化激活阳离子电流（Ih）增加。
正常小鼠给予MGO后Ih上调。
MGO与轴突兴奋性异常有关。糖尿病性多发性神经病变中的超兴奋性可能至少部分是由功能失调的轴突超极化激活环核苷酸门控（HCN）通道引起的。未来对大量糖尿病患者的研究将阐明这一假说。
