National Engineering Laboratory for Brain-inspired Intelligence Technology and Application, School of Information Science and Technology, University of Science and Technology of China, Anhui, China.
Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China.
Sci Adv. 2022 Jun 10;8(23):eabn5345. doi: 10.1126/sciadv.abn5345. Epub 2022 Jun 8.
Glucagon-like peptide-1 (GLP-1) regulates energy homeostasis via activation of the GLP-1 receptors (GLP-1Rs) in the central nervous system. However, the mechanism by which the central GLP-1 signal controls blood glucose levels, especially in different nutrient states, remains unclear. Here, we defined a population of glucose-sensing GLP-1R neurons in the dorsomedial hypothalamic nucleus (DMH), by which endogenous GLP-1 decreases glucose levels via the cross-talk between the hypothalamus and pancreas. Specifically, we illustrated the sufficiency and necessity of DMH in glucose regulation. The activation of the DMH neurons is mediated by a cAMP-PKA-dependent inhibition of a delayed rectifier potassium current. We also dissected a descending control of DMH -dorsal motor nucleus of the vagus nerve (DMV)-pancreas activity that can regulate glucose levels by increasing insulin release. Thus, our results illustrate how central GLP-1 action in the DMH can induce a nutrient state-dependent reduction in blood glucose level.
胰高血糖素样肽-1（GLP-1）通过激活中枢神经系统中的 GLP-1 受体（GLP-1R）来调节能量稳态。然而，中枢 GLP-1 信号控制血糖水平的机制，特别是在不同营养状态下，仍不清楚。在这里，我们通过研究发现，下丘脑腹内侧核（DMH）中存在一群葡萄糖感应型 GLP-1R 神经元，内源性 GLP-1 通过下丘脑和胰腺之间的串扰降低血糖水平。具体来说，我们说明了 DMH 在葡萄糖调节中的充分性和必要性。DMH 神经元的激活是通过 cAMP-PKA 依赖性抑制延迟整流钾电流来介导的。我们还剖析了 DMH-迷走神经背核（DMV）-胰腺活性的下行控制，通过增加胰岛素释放来调节血糖水平。因此，我们的研究结果阐明了中枢 GLP-1 在 DMH 中的作用如何诱导血糖水平的营养状态依赖性降低。
