Purpose of review: Past studies in humans and animals have shown that low blood glucose concentrations due to fasting negatively interfere with the ability to mount a hypothalamus-pituitary-adrenal (HPA) axis response to psychological stress or to pharmacological activation, respectively. This contradicts the classical view of the proposed primary glucocorticoid function of providing the individual with energy in fight-or-flight situations.
Recent findings: Not many studies have followed up on this phenomenon in recent years, but our understanding of how appetite and satiety is regulated has significantly improved. Many of the neuropeptides involved in regulation of energy homeostasis interact with key areas of the HPA axis. The majority of orexigenic peptides have been shown to activate the HPA axis, while some anorexic peptides negatively modulate HPA axis activation and others also stimulate it.
Summary: The effects of orexigenic peptides on the HPA axis are incompatible with the phenomenon of blunted HPA axis activity in states of low energy available, while the fact that some anorexigenic peptides activate the HPA axis might point to a permissive role. In conclusion, current data insufficiently explain negative HPA axis modulation by low glucose levels.