The ventromedial hypothalamus (VMH) is a critical neural node that senses blood glucose and promotes glucose utilization or mobilization during hypoglycemia. The VMH neurons that control these distinct physiologic processes are largely unknown. Here, we show that melanocortin 3 receptor (Mc3R)-expressing VMH neurons (VMH^MC3R) sense glucose changes both directly and indirectly via altered excitatory input. We identify presynaptic nodes that potentially regulate VMH^MC3R neuronal activity, including inputs from proopiomelanocortin (POMC)-producing neurons in the arcuate nucleus. We find that VMH^MC3R neuron activation blunts, and their silencing enhances glucose excursion following a glucose load. Overall, these findings demonstrate that VMH^MC3R neurons are a glucose-responsive hypothalamic subpopulation that promotes glucose disposal upon activation; this highlights a potential site for targeting dysregulated glycemia.

下丘脑腹内侧（VMH）是感知血糖并在低血糖期间促进葡萄糖利用或动员的关键神经节点。控制这些不同生理过程的 VMH 神经元在很大程度上是未知的。在这里，我们发现表达黑皮质素 3 受体 ( Mc3R ) 的 VMH 神经元 (VMH ^MC3R ) 通过改变兴奋性输入直接或间接感知葡萄糖变化。我们确定了可能调节 VMH ^MC3R神经元活动的突触前节点，包括来自弓状核中产生阿片黑皮素原 (POMC) 的神经元的输入。我们发现VMH ^MC3R神经元的激活减弱，它们的沉默会增强葡萄糖负荷后的葡萄糖偏移。总体而言，这些发现表明 VMH ^MC3R神经元是葡萄糖反应性下丘脑亚群，在激活后可促进葡萄糖处理；这凸显了针对血糖失调的潜在位点。