Functional identification of a neurocircuit regulating blood glucose

Abstract

Previous studies implicate the hypothalamic ventromedial nucleus (VMN) in glycemic control. Here, we report that selective inhibition of the subset of VMN neurons that express the transcription factor steroidogenic-factor 1 (VMNSF1 neurons) blocks recovery from insulin-induced hypoglycemia whereas, conversely, activation of VMNSF1 neurons causes diabetes-range hyperglycemia. Moreover, this hyperglycemic response is reproduced by selective activation of VMNSF1 fibers projecting to the anterior bed nucleus of the stria terminalis (aBNST), but not to other brain areas innervated by VMNSF1 neurons. We also report that neurons in the lateral parabrachial nucleus (LPBN), a brain area that is also implicated in the response to hypoglycemia, make synaptic connections with the specific subset of glucoregulatory VMNSF1 neurons that project to the aBNST. These results collectively establish a physiological role in glucose homeostasis for VMNSF1 neurons and suggest that these neurons are part of an ascending glucoregulatory LPBN→VMNSF1→aBNST neurocircuit.