PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia.
PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia.
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DOI：
10.3389/fendo.2018.00632
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发表时间：
2018
影响因子：
5.2
通讯作者：
Luckman SM
中科院分区：
文献类型：
--
作者：
Khodai T;Nunn N;Worth AA;Feetham CH;Belle MDC;Piggins HD;Luckman SM
工作背景：葡萄糖敏感神经元位于大脑的几个部分，但集中在下丘脑腹内侧核（VMH）。这些VMH神经元在葡萄糖稳态中的重要性是公认的，然而，对它们的个体身份知之甚少。在本研究中，我们确定了一个独特的葡萄糖敏感人口的VMH和探讨其在葡萄糖调节网络。研究方法：采用膜片钳电生理学方法，对Pacap-cre：：EYFP细胞的VMH内外的垂体腺苷酸环化酶激活肽（PACAP）神经元的葡萄糖敏感能力进行了研究。我们还映射了这些神经元的传出投射，使用顺行和逆行追踪技术。最后，为了在体内测试PACAPVMH的功能，我们使用DREADD技术并测量全身反应。结果：我们证明，PACAP神经元内（PACAPVMH），而不是外的VMH是固有的葡萄糖抑制（GI）。解剖追踪技术表明，PACAPVMH神经元投射到几个可以影响自主输出的区域。在体内，这些神经元的化学刺激抑制胰岛素分泌，导致葡萄糖耐量降低，暗示它们在全身葡萄糖调节中的作用。结论：这些发现是重要的，因为他们确定，第一次，一个特定的VMH神经元群体参与葡萄糖稳态。识别VMH中的不同葡萄糖感知群体将有助于将葡萄糖调节的不同分支拼凑在一起，提供关于对葡萄糖代谢紊乱（包括低血糖）的中枢反应的重要信息。
Background: Glucose-sensing neurons are located in several parts of the brain, but are concentrated in the ventromedial nucleus of the hypothalamus (VMH). The importance of these VMH neurons in glucose homeostasis is well-established, however, little is known about their individual identity. In the present study, we identified a distinct glucose-sensing population in the VMH and explored its place in the glucose-regulatory network. Methods: Using patch-clamp electrophysiology on Pacap-cre::EYFP cells, we explored the glucose-sensing ability of the pituitary adenylate cyclase-activating peptide (PACAP) neurons both inside and outside the VMH. We also mapped the efferent projections of these neurons using anterograde and retrograde tracing techniques. Finally, to test the functionality of PACAPVMH in vivo, we used DREADD technology and measured systemic responses. Results: We demonstrate that PACAP neurons inside (PACAPVMH), but not outside the VMH are intrinsically glucose inhibited (GI). Anatomical tracing techniques show that PACAPVMH neurons project to several areas that can influence autonomic output. In vivo, chemogenetic stimulation of these neurons inhibits insulin secretion leading to reduced glucose tolerance, implicating their role in systemic glucose regulation. Conclusion: These findings are important as they identify, for the first time, a specific VMH neuronal population involved in glucose homeostasis. Identifying the different glucose-sensing populations in the VMH will help piece together the different arms of glucose regulation providing vital information regarding central responses to glucose metabolic disorders including hypoglycaemia.