Discovering an adrenal-independent pathway for rapid glucose release during stress can transform our understanding of glucose regulation and open new avenues for treating metabolic disorders.
A new study by the University of Science and Technology of China (USTC) has unveiled a novel, adrenal-independent pathway to mediate stress-induced glucose release. Published in the journal Nature Communications, this discovery could revolutionize our understanding of glucose regulation and bring new therapeutic targets for stress-related metabolic disorders into focus.
When animals experience stress, their central nervous system rapidly triggers the release of blood glucose to tackle potential threats. Traditionally, this response has been attributed to the hypothalamus-pituitary-adrenal (HPA) axis or the sympathetic-adrenal-medullary (SAM) axis. However, both these mechanisms involve the adrenal glands and exhibit notable time delays, which are not ideal for the immediate needs posed by stress.
Led by Ji Liu, a professor at USTC’s School of Earth and Space Sciences, the researchers sought to determine whether there was an alternative pathway that could facilitate quicker glucose release during stress.
Utilizing advanced techniques such as virus tracing and optogenetic manipulations, they mapped the neural pathway from the paraventricular nucleus (PVNCRH) to the ventromedial hypothalamus (VMH) in mice. Their experiments revealed that stimulating CRH neurons in the PVN quickly elevated glucose levels. Moreover, they found that activating CRH receptors, particularly the CRH receptor subtype 2 (CRHR2), was crucial for glucose regulation during stress.
Further exploration showed that sympathetic innervation of the liver significantly impacts CRH in glucose modulation. The team activated CRHR2 in VMH via optogenetic stimulation and established that these neurons received projections from CRH, thereby regulating hepatic gluconeogenesis through sympathetic innervation. This finding unveiled an adrenal-independent neural pathway for rapid glucose release.
The significance of this discovery extends to its potential therapeutic applications. By comparing the time windows of adrenal-dependent and adrenal-independent regulation, the team concluded that the immediate phase of glucose release is managed by the hypothalamus-sympathetic-liver (HSL) axis, whereas the delayed phase is regulated by adrenal hormones.
This study illuminates a previously unknown mechanism in the rapid regulation of glucose during stress. Its findings provide critical insights into glucose homeostasis and point toward potential therapeutic targets for stress-related metabolic disorders.
These revelations could reshape therapeutic approaches for managing stress-induced metabolic disorders and enhance our broader understanding of glucose homeostasis.