Ventromedial hypothalamic nucleus neuronal subset regulates blood glucose independently of insulin
Ventromedial hypothalamic nucleus neuronal subset regulates blood glucose independently of insulin
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DOI：
10.1172/jci134135
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发表时间：
2020-06-01
影响因子：
15.9
通讯作者：
Myers, Martin G., Jr.
中科院分区：
文献类型：
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作者：
Flak, Jonathan N.;Goforth, Paulette B.;Myers, Martin G., Jr.
为了从腹内侧下丘脑核 (VMN) 的多种功能细胞类型中识别特异性升高血糖的神经元，我们研究了表达胆囊收缩素受体 B（表达 CCKBR）的 VMN 葡萄糖升高臂旁核神经元靶标。这些 VMNCCKBR 神经元的激活会增加血糖。此外，虽然沉默更广泛的 VMN 会减少能量消耗并促进体重增加，但不会改变血糖水平，但沉默 VMNCCKBR 神经元会减少肝脏葡萄糖的产生，独立于胰岛素降低血糖，而不会改变能量平衡。沉默 VMNCCKBR 神经元还会损害对胰岛素引起的低血糖和糖缺乏的反调节反应，并复制低血糖相关的自主神经衰竭。因此，VMNCCKBR 细胞代表了 VMN 细胞的一个特殊亚群，其功能是升高葡萄糖。这些细胞不仅介导对低血糖的稳态反应，而且还以不依赖于胰岛素的方式调节血糖的稳态设定点，这与大脑在不依赖于胰岛素的葡萄糖稳态控制中的作用一致。
To identify neurons that specifically increase blood glucose from among the diversely functioning cell types in the ventromedial hypothalamic nucleus (VMN), we studied the cholecystokinin receptor B-expressing (CCKBR-expressing) VMN targets of glucose-elevating parabrachial nucleus neurons. Activation of these VMNCCKBR neurons increased blood glucose. Furthermore, although silencing the broader VMN decreased energy expenditure and promoted weight gain without altering blood glucose levels, silencing VMNCCKBR neurons decreased hlepatic glucose production, insulin-independently decreasing blood glucose without altering energy balance. Silencing VMNCCKBR neurons also impaired the counterregulatory response to insulin-induced hypoglycemia and glucoprivation and replicated hypoglycemia-associated autonomic failure. Hence, VMNCCKBR cells represent a specialized subset of VMN cells that function to elevate glucose. These cells not only mediate the allostatic response to hypoglycemia but also modulate the homeostatic setpoint for blood glucose in an insulin-independent manner, consistent with a role for the brain in the insulin-independent control of glucose homeostasis.