Sensory and autonomic function and structure in footpads of a diabetic mouse model.
Sensory and autonomic function and structure in footpads of a diabetic mouse model.
复制标题
糖尿病小鼠模型的脚垫中的感觉和自主功能和结构。
DOI：
10.1038/srep41401
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发表时间：
2017-01-27
影响因子：
4.6
通讯作者：
Farah MH
中科院分区：
文献类型：
--
作者：
Liu Y;Sebastian B;Liu B;Zhang Y;Fissel JA;Pan B;Polydefkis M;Farah MH
感觉和自主神经病变影响大多数II型糖尿病患者。在临床上，自主神经评估通常集中在运动功能上，但很少在动物模型中进行评估。我们进行了形态和功能研究，以评估db/db II型糖尿病小鼠模型中大的有髓轴突和小的无髓轴突。我们观察到，与对照组db/+小鼠相比，db/db组小鼠足垫汗腺的自主神经支配显著减少，而且与相邻表皮的表皮内感觉神经支配减少相比，这一缺陷更为严重。此外，早在6周大的时候，db/db小鼠与对照组相比形成的汗滴明显减少，这段时间在db/db和db/+小鼠对大型有髓感觉神经和运动神经的研究中没有观察到统计上的差异。与对照组相比，db/db组小鼠的汗滴形成速度明显较慢，汗滴大小更大，变化更大。在6个月大的对照组中，毛果芸香碱和甘草次酸分别增加和减少出汗，而db/db小鼠对药物操作没有反应。我们的发现表明，自主神经病变是db/db模型中早期和显著的缺陷，并对开发外周糖尿病神经病变的治疗方法有一定的意义。
Sensory and autonomic neuropathy affects the majority of type II diabetic patients. Clinically, autonomic evaluation often focuses on sudomotor function yet this is rarely assessed in animal models. We undertook morphological and functional studies to assess large myelinated and small unmyelinated axons in the db/db type II diabetes mouse model. We observed that autonomic innervation of sweat glands in the footpads was significantly reduced in db/db mice compared to control db/+ mice and this deficit was greater compared to reductions in intraepidermal sensory innervation of adjacent epidermis. Additionally, db/db mice formed significantly fewer sweat droplets compared to controls as early as 6 weeks of age, a time when no statistical differences were observed electrophysiologically between db/db and db/+ mice studies of large myelinated sensory and motor nerves. The rate of sweat droplet formation was significantly slower and the sweat droplet size larger and more variable in db/db mice compared to controls. Whereas pilocarpine and glycopyrrolate increased and decreased sweating, respectively, in 6 month-old controls, db/db mice did not respond to pharmacologic manipulations. Our findings indicate autonomic neuropathy is an early and prominent deficit in the db/db model and have implications for the development of therapies for peripheral diabetic neuropathy.