Glucose homeostasis is mainly under the control of the pancreatic islet hormones insulin and glucagon, which, respectively, stimulate glucose uptake and utilization by liver, fat, and muscle or glucose production by the liver. The balance between the secretion of these hormones is under the control of blood glucose concentrations. Indeed, pancreatic islet b-cells and a-cells can sense variations in glycemia and respond by an appropriate secretory response to restore euglycemia. However, the secretory activity of these cells is also under multiple additional metabolic, hormonal, and neuronal signals that combine to ensure the perfect control of glycemia over a lifetime. The central nervous system (CNS), which has an almost absolute requirement for glucose as a source of metabolic energy and, thus, a vital interest in ensuring that glycemic levels never fall below ~5mM, is equipped with populations of neurons responsive to changes in glucose concentrations. These neurons control pancreatic islet cells secretion activity in multiple ways: through both branches of the autonomic nervous system, through the hypothalamic-pituitary-adrenal axis, and by secreting vasopressin (AVP) in the blood at the level of the posterior pituitary. Here, we will present the autonomic innervation of the pancreatic islets; the mechanisms of neurons activation by a rise or a fall in glucose concentration; how current viral tracing, chemogenetic, and optogenetic techniques allow to integrate specific glucose sensing neurons in defined neuronal circuits that control endocrine pancreas function. Finally, how genetic screens in mice can untangle the diversity of the hypothalamic mechanisms controlling the response to hypoglycemia.

中文翻译：

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控制胰岛素和胰高血糖素分泌的神经元葡萄糖传感机制和电路


葡萄糖稳态主要受胰岛激素胰岛素和胰高血糖素的控制，它们分别刺激肝脏、脂肪和肌肉的葡萄糖摄取和利用或肝脏产生葡萄糖。这些激素的分泌之间的平衡受到血糖浓度的控制。事实上，胰岛 b 细胞和 a 细胞可以感知血糖的变化，并通过适当的分泌反应来恢复血糖正常。然而，这些细胞的分泌活动还受到多种额外代谢、激素和神经元信号的影响，这些信号结合起来确保一生中血糖的完美控制。中枢神经系统 (CNS) 几乎绝对需要葡萄糖作为代谢能量的来源，因此，确保血糖水平永远不会低于约 5mM 至关重要，它配备了对葡萄糖变化做出反应的神经元群。葡萄糖浓度。这些神经元以多种方式控制胰岛细胞的分泌活动：通过自主神经系统的两个分支，通过下丘脑-垂体-肾上腺轴，以及通过在垂体后叶水平的血液中分泌加压素（AVP）。在这里，我们将介绍胰岛的自主神经支配；葡萄糖浓度升高或降低导致神经元激活的机制；当前的病毒追踪、化学遗传学和光遗传学技术如何将特定的葡萄糖传感神经元整合到控制内分泌胰腺功能的确定的神经元回路中。最后，小鼠的遗传筛选如何解开控制低血糖反应的下丘脑机制的多样性。