Hypothalamus-sympathetic-liver axis mediates the early phase of stress-induced hyperglycemia

Hypothalamic corticotropin-releasing hormone (CRH) is a central driver of stress responses. However, how the CRH neurons regulate glucose release during the different stages of stress remains unclear. Here, we showed that adrenal activity is required for the delayed stage, but not for early stage of stress induced glucose release. Instead, a CRH initiated hypothalamus-sympathetic-liver (HSL) axis activity responds for the early stage of glucose release during stress. In the HSL pathway, CRH activates CRH receptor subtype 2 (CRHR2) in the ventromedial hypothalamus (VMH) by inducing GABAA receptor β3 subunit phosphorylation at S408/409 to reduce GABAA receptor membrane recruitment. Blocking the activity of HSL axis causes an abnormal foot-shock stress and predatory cue-evoked flight responses. We discovered that the adrenal activity dependent and independent pathway control the different stages of energy supply respectively when facing the potential threats

下丘脑促肾上腺皮质激素释放激素（CRH）是应激反应的中心驱动力。然而，CRH神经元如何在应激的不同阶段调节葡萄糖释放尚不明确。在本研究中，我们发现肾上腺活动对于应激诱导的葡萄糖释放的延迟阶段是必需的，而对于早期阶段则不是。相反，由CRH启动的下丘脑-交感神经-肝脏（HSL）轴活动负责应激早期葡萄糖释放。在HSL通路中，CRH通过诱导GABAA受体β3亚基在S408/409位点的磷酸化，减少GABAA受体膜募集，从而激活腹中核（VMH）中的CRH受体亚型2（CRHR2）。阻断HSL轴的活动会导致异常的足部电击应激和捕食者线索引发的飞行反应。我们发现，肾上腺活动依赖性和独立性途径分别控制面对潜在威胁时能量供应的不同阶段。