Systemic Glucoregulation by Glucose-Sensing Neurons in the Ventromedial Hypothalamic Nucleus (VMH).
Systemic Glucoregulation by Glucose-Sensing Neurons in the Ventromedial Hypothalamic Nucleus (VMH).
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DOI：
10.1210/js.2016-1104
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发表时间：
2017-05-01
影响因子：
4.1
通讯作者：
Minokoshi Y
中科院分区：
文献类型：
--
作者：
Shimazu T;Minokoshi Y
下丘脑腹内侧核(VMH)通过传出交感神经支配和神经内分泌机制调节肝脏葡萄糖的产生以及周围组织(包括骨骼肌和棕色脂肪组织)对葡萄糖的吸收和利用。瘦素对VMH神经元的作用也通过交感神经系统增加特定外周组织对葡萄糖的摄取，从而改善胰岛素敏感性。另一方面，VMH神经元的亚群，如那些表达类固醇生成因子1(SF1)的神经元，感觉周围葡萄糖浓度的变化，其特征是葡萄糖兴奋(GE)和葡萄糖抑制(GI)神经元，其动作电位频率分别随着葡萄糖水平的增加而增加和减少。然而，VMH中的这些葡萄糖敏感神经元(GE和GI)如何对全身糖调节做出贡献仍然知之甚少。在这篇综述中，我们提供了历史背景，并讨论了与VMH神经元的糖调节相关的最新进展。特别是，文章描述了GE神经元在控制外周葡萄糖利用和胰岛素敏感性中的作用，这依赖于神经元的线粒体解偶联蛋白2，以及GI神经元通过低血糖诱导的逆调节机制控制肝脏葡萄糖的产生。本文描述了VMH神经元的糖调节作用，特别是GE神经元在控制外周葡萄糖利用中的作用以及GI神经元在肝脏葡萄糖产生中的作用。
The ventromedial hypothalamic nucleus (VMH) regulates glucose production in the liver as well as glucose uptake and utilization in peripheral tissues, including skeletal muscle and brown adipose tissue, via efferent sympathetic innervation and neuroendocrine mechanisms. The action of leptin on VMH neurons also increases glucose uptake in specific peripheral tissues through the sympathetic nervous system, with improved insulin sensitivity. On the other hand, subsets of VMH neurons, such as those that express steroidogenic factor 1 (SF1), sense changes in the ambient glucose concentration and are characterized as glucose-excited (GE) and glucose-inhibited (GI) neurons whose action potential frequency increases and decreases, respectively, as glucose levels rise. However, how these glucose-sensing (GE and GI) neurons in the VMH contribute to systemic glucoregulation remains poorly understood. In this review, we provide historical background and discuss recent advances related to glucoregulation by VMH neurons. In particular, the article describes the role of GE neurons in the control of peripheral glucose utilization and insulin sensitivity, which depend on mitochondrial uncoupling protein 2 of the neurons, as well as that of GI neurons in the control of hepatic glucose production through hypoglycemia-induced counterregulatory mechanisms. Our article describes glucoregulation by VMH neurons, in particular the role of GE neurons in the control of peripheral glucose utilization and that of GI neurons in hepatic glucose production.