Hypothalamic Orexin Stimulates Feeding-Associated Glucose Utilization in Skeletal Muscle via Sympathetic Nervous System
Hypothalamic Orexin Stimulates Feeding-Associated Glucose Utilization in Skeletal Muscle via Sympathetic Nervous System
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DOI：
10.1016/j.cmet.2009.09.013
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发表时间：
2009-12-02
期刊：
影响因子：
29
通讯作者：
Minokoshi, Yasuhiko
中科院分区：
文献类型：
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作者：
Shiuchi, Tetsuya;Haque, Mohammad Shahidul;Minokoshi, Yasuhiko
含有食欲素（下丘脑分泌素）的下丘脑神经元在动机行为和主动醒来时被激活。我们发现，通过激活交感神经系统，将食欲素-A注射到小鼠或大鼠的腹内侧下丘脑（VMH）中，可以增加葡萄糖摄取，并促进骨骼肌中胰岛素诱导的葡萄糖摄取和糖原合成，但不会促进白色脂肪组织中的葡萄糖摄取和糖原合成。食欲素的这些作用在缺乏β-肾上腺素能受体的小鼠中减弱，但通过在骨骼肌的肌细胞和非肌细胞中强制表达β(2)-肾上腺素能受体而恢复。食欲素神经元被条件甜味激活并直接兴奋VMH神经元，从而增加肌肉葡萄糖代谢及其胰岛素敏感性。因此，VMH 中的食欲素及其受体通过激活肌肉交感神经和 β(2)-肾上腺素能信号传导，在与高度动机行为相关的肌肉葡萄糖代谢调节中发挥着关键作用。
Hypothalamic neurons containing orexin (hypocretin) are activated during motivated behaviors and active waking. We show that injection of orexin-A into the ventromedial hypothalamus (VMH) of mice or rats increased glucose uptake and promoted insulin-induced glucose uptake and glycogen synthesis in skeletal muscle, but not in white adipose tissue, by activating the sympathetic nervous system. These effects of orexin were blunted in mice lacking beta-adrenergic receptors but were restored by forced expression of the beta(2)-adrenergic receptor in both myocytes and nonmyocyte cells of skeletal muscle. Orexin neurons are activated by conditioned sweet tasting and directly excite VMH neurons, thereby increasing muscle glucose metabolism and its insulin sensitivity. Orexin and its receptor in VMH thus play a key role in the regulation of muscle glucose metabolism associated with highly motivated behavior by activating muscle sympathetic nerves and beta(2)-adrenergic signaling.