Accumulation of sorbitol in the sciatic nerve modulates circadian properties of diabetes-induced neuropathic pain hypersensitivity in a diabetic mouse model
Accumulation of sorbitol in the sciatic nerve modulates circadian properties of diabetes-induced neuropathic pain hypersensitivity in a diabetic mouse model
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DOI：
10.1016/j.bbrc.2018.05.209
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发表时间：
2018-09-03
影响因子：
3.1
通讯作者：
Ohdo, Shigehiro
中科院分区：
文献类型：
--
作者：
Akamine, Takahiro;Kusunose, Naoki;Ohdo, Shigehiro
糖尿病神经病变的疼痛强度随昼夜节律时间变化而变化。众所周知，糖尿病有两种不同的类型，根据病因进行区分。先前的研究尚未比较 I 型和 II 型糖尿病之间糖尿病神经病变疼痛强度的昼夜节律特性。在这项研究中，我们证明，II 型糖尿病 db/db 小鼠模型中糖尿病周围神经病变的疼痛强度表现出显着的昼夜振荡，但在链脲佐菌素 (STZ) 诱导的 I 型糖尿病小鼠模型中未检测到这种时间依赖性振荡。多元醇途径诱导的山梨醇在周围神经细胞中的积累会抑制 Na+/K+-ATP 酶活性，而 Na+/K+-ATP 酶活性与糖尿病神经病变的疼痛强度有关。在 db/db 小鼠中，山梨醇在周围神经细胞中的积累表现出显着的昼夜振荡。此外，这些小鼠的疼痛强度和Na+/K+-ATP酶活性在山梨醇积累的峰值时间降低。尽管 STZ 诱导的糖尿病小鼠也表现出山梨醇积累和 Na+/K+-ATP 酶功能障碍，但这些测量值并不以时间依赖性方式振荡。这些发现揭示了 I 型和 II 型糖尿病小鼠模型中疼痛过敏的昼夜节律特性的差异，并为开发治疗糖尿病神经病变的新方法提供了思路。 (C) 2018 Elsevier Inc. 保留所有权利。
The intensity of pain in diabetic neuropathy varies in a circadian time-dependent manner. It is well known that diabetes has two distinct types, which are differentiated based on the cause of the disease. Previous studies have yet to compare the circadian properties of the pain intensity of diabetic neuropathy between type I and type II diabetes. In this study, we demonstrated that the pain intensity of diabetic peripheral neuropathy in a db/db mouse model of type II diabetes showed a significant diurnal oscillation, but such time-dependent oscillation was not detected in a streptozotocin (STZ)-induced type I diabetic mouse model. The polyol pathway-induced accumulation of sorbitol in peripheral nerve cells suppresses Na+/K+-ATPase activity, which is associated with the intensity of pain in diabetic neuropathy. In db/db mice, this accumulation of sorbitol in peripheral nerve cells showed significant diurnal oscillation. In addition, pain intensity and Na+/K+-ATPase activity were decreased at the peak time of sorbitol accumulation in these mice. Although STZ-induced diabetic mice also showed sorbitol accumulation and Na+ /K+-ATPase dysfunction, these measures did not oscillate in a time-dependent manner. These findings reveal differences in the circadian properties of pain hypersensitivity in mouse models of type I and type II diabetes, and also provide ideas for developing novel approaches to the management of diabetic neuropathy. (C) 2018 Elsevier Inc. All rights reserved.