Division of Endocrinology and Metabolism, Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Cell Metab. 2009 Dec;10(6):466-80. doi: 10.1016/j.cmet.2009.09.013.
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.
下丘脑含食欲素（下丘脑分泌素）的神经元在动机性行为和活跃清醒时被激活。我们发现，在小鼠或大鼠的腹内侧下丘脑（VMH）注射食欲素-A 会通过激活交感神经系统，增加葡萄糖摄取，并促进胰岛素诱导的骨骼肌葡萄糖摄取和糖原合成，但不会增加白色脂肪组织的葡萄糖摄取和糖原合成。在缺乏β-肾上腺素能受体的小鼠中，食欲素的这些作用减弱，但通过在骨骼肌的心肌细胞和非心肌细胞中强制表达β2-肾上腺素能受体而得到恢复。食欲素神经元被条件性甜味觉激活，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β2-肾上腺素能信号传导，在调节与高度动机性行为相关的肌肉葡萄糖代谢中发挥关键作用。
