Deletion of the insulin receptor in sensory neurons increases pancreatic insulin levels.
Deletion of the insulin receptor in sensory neurons increases pancreatic insulin levels.
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DOI：
10.1016/j.expneurol.2018.04.002
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发表时间：
2018-07
影响因子：
5.3
通讯作者：
Wright DE
中科院分区：
文献类型：
--
作者：
Grote CW;Wilson NM;Katz NK;Guilford BL;Ryals JM;Novikova L;Stehno-Bittel L;Wright DE
已知胰岛素具有神经营养特性，失去对感觉神经元的胰岛素支持可能会导致外周糖尿病神经病变(PDN)。在这里，产生了外周感觉神经元缺乏胰岛素受体的转基因小鼠(SNIRKO小鼠)，以确定感觉神经元胰岛素信号中断是否在PDN的发展中起关键作用，以及SNIRKO小鼠是否由于胰岛素神经营养支持减少而出现PDN症状。我们的结果表明，SNIRKO小鼠血糖正常，在感觉运动行为、神经传导速度或表皮内神经纤维密度方面从未出现明显变化。然而，SNIRKO小鼠表现出血清胰岛素水平升高，葡萄糖耐量增加，胰腺朗格汉斯胰岛胰岛素含量增加。这些结果支持了一种观点，即胰岛的感觉神经支配是调节胰岛功能的关键，感觉神经元胰岛素信号的负反馈回路保持了这一调节的平衡。我们的结果表明，感觉神经元中胰岛素受体的丢失不会导致周围神经功能障碍。SNIRKO小鼠将是研究感觉神经元胰岛素信号的有力工具，并可能为感觉神经元在修改胰岛生理中所起的作用提供独特的见解。
Insulin is known to have neurotrophic properties and loss of insulin support to sensory neurons may contribute to peripheral diabetic neuropathy (PDN). Here, genetically-modified mice were generated in which peripheral sensory neurons lacked the insulin receptor (SNIRKO mice) to determine whether disrupted sensory neuron insulin signaling plays a crucial role in the development of PDN and whether SNIRKO mice develop symptoms of PDN due to reduced insulin neurotrophic support. Our results revealed that SNIRKO mice were euglycemic and never displayed significant changes in a wide range of sensorimotor behaviors, nerve conduction velocity or intraepidermal nerve fiber density. However, SNIRKO mice displayed elevated serum insulin levels, glucose intolerance, and increased insulin content in the islets of Langerhans of the pancreas. These results contribute to the growing idea that sensory innervation of pancreatic islets is key to regulating islet function and that a negative feedback loop of sensory neuron insulin signaling keeps this regulation in balance. Our results suggest that a loss of insulin receptors in sensory neurons does not lead to peripheral nerve dysfunction. The SNIRKO mice will be a powerful tool to investigate sensory neuron insulin signaling and may give a unique insight into the role that sensory neurons play in modifying islet physiology.
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影响因子：
7.1
作者：
Grote CW;Groover AL;Ryals JM;Geiger PC;Feldman EL;Wright DE
通讯作者：
Wright DE
影响因子：
--
作者：
Guilford, B. L.;Ryals, J. M.;Wright, D. E.
通讯作者：
Wright, D. E.
影响因子：
5
作者：
Gram, DX;Hansen, AJ;Ahrén, D
通讯作者：
Ahrén, D
DOI：
10.1073/pnas.1014411108
发表时间：
2011-02-22
影响因子：
11.1
作者：
da Silva, Susana;Hasegawa, Hiroshi;Wang, Fan
通讯作者：
Wang, Fan
影响因子：
5.3
作者：
Jack, M. M.;Ryals, J. M.;Wright, D. E.
通讯作者：
Wright, D. E.