A Central Catecholaminergic Circuit Controls Blood Glucose Levels during Stress

Abstract

Stress-induced hyperglycemia is a fundamental adaptive response that mobilizes energy stores in response to threats. Here, our examination of the contributions of the central catecholaminergic (CA) neuronal system to this adaptive response revealed that CA neurons in the ventrolateral medulla (VLM) control stress-induced hyperglycemia. Ablation of VLM CA neurons abolished the hyperglycemic response to both physical and psychological stress, whereas chemogenetic activation of these neurons was sufficient to induce hyperglycemia. We further found that CA neurons in the rostral VLM, but not those in the caudal VLM, cause hyperglycemia via descending projections to the spinal cord. Monosynaptic tracing experiments showed that VLM CA neurons receive direct inputs from multiple stress-responsive brain areas. Optogenetic studies identified an excitatory PVN-VLM circuit that induces hyperglycemia. This study establishes the central role of VLM CA neurons in stress-induced hyperglycemia and substantially expands our understanding of the central mechanism that controls glucose metabolism.

C1 neurons: a nodal point for stress?

“…; Zhao et al . ). The C1 cells that innervate the dorsal motor nucleus of the vagus (DMV) might be a third major functional group.…”

“…Thus, a relatively normal BP or glycaemia is maintained without C1 cells, but C1 cell activation is required for BP stability and glucose release during an acute cardiovascular stress (see also Zhao et al . ).…”

“…; Zhao et al . ). By way of caveat, these gain‐of‐function experiments demonstrate that C1 cell activation has the potential to contribute to arousal from sleep.…”

“…; Schiltz & Sawchenko, ; Zhao et al . ). In mice, stress‐induced glucose release requires the integrity of the C1 cells and of the adrenal gland; it is suppressed when the C1 cells are selectively silenced and mimicked by their activation (Zhao et al .…”

“…In mice, stress‐induced glucose release requires the integrity of the C1 cells and of the adrenal gland; it is suppressed when the C1 cells are selectively silenced and mimicked by their activation (Zhao et al . ). Most probably, stress increases glucose release by activating those C1 cells that control the release of adrenaline from the adrenal medulla (Verberne et al .…”