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