Laboratoire de Physiologie et Physiopathologie du Système Nerveux Somato-Moteur et Neurovégétatif, Aix-Marseille Université, Marseille, France.
J Neuroendocrinol. 2013 Jan;25(1):1-13. doi: 10.1111/j.1365-2826.2012.02375.x.
Nesfatin-1 is a recently identified 82 amino acid peptide shown to have an anorexigenic effect on rodents when administrered centrally and peripherally. Nesfatin-1 is expressed not only in neurones of various brain areas, including the hypothalamic and brainstem nuclei, but also in peripheral organs, such as the stomach and the pancreas. Nesfatinergic neurones were reported to participate in the regulation of satiety signals and in the responses to other stimuli, including restraint stress, abdominal surgery, and lipopolysaccharide-induced inflammation. The present study aimed to investigate whether NUCB2/nesfatin-1 expressing neurones also take part in the central signalling activated in response to hypoglycaemia and therefore are involved in central glucose sensing. Using immunolabelling methods based on the detection of the neuronal activation marker c-Fos and of nesfatin-1, we showed that peripheral injection of insulin induced a strong activation of nesfatin-1-expressing neurones in the brain vagal-regulatory nuclei, including the arcuate nucleus, paraventricular nucleus, lateral hypothalamic area, dorsal motor nucleus of the vagus (DMNX) and nucleus of the tractus solitarius. In response to intracellular glucopaenia induced by i.p. or i.c.v. 2-deoxyglucose injection, the c-Fos/nesfatin-1 colocalisations observed at the hypothalamic and brainstem levels were similar to those observed after insulin-induced hypoglycaemia. Moreover, using Fluorogold as a retrograde tracer, we showed that nesfatinergic preganglionic DMNX neurones activated by hypoglycaemia target the stomach and the pancreas. Taken together, these results suggest that a subpopulation of nesfatinergic neurones belongs to the central network activated by hypoglycaemia, and that nesfatin-1 participates in the triggering of physiological and hormonal counter-regulations observed in response to hypoglycaemia.
内脂素-1 是一种新发现的 82 个氨基酸肽，当在中枢和外周给药时，它对啮齿动物有厌食作用。内脂素-1 不仅在各种脑区的神经元中表达，包括下丘脑和脑干核，而且在外周器官中表达，如胃和胰腺。据报道，内脂素能神经元参与饱腹感信号的调节，并对其他刺激做出反应，包括束缚应激、腹部手术和脂多糖诱导的炎症。本研究旨在探讨 NUCB2/内脂素-1 表达神经元是否也参与中枢对低血糖的信号激活，从而参与中枢葡萄糖感应。使用基于神经元激活标志物 c-Fos 和内脂素-1 检测的免疫标记方法，我们发现外周注射胰岛素会强烈激活脑迷走神经调节核中的内脂素-1 表达神经元，包括弓状核、室旁核、外侧下丘脑区域、迷走神经背核（DMNX）和孤束核。在腹腔或脑室内注射 2-脱氧葡萄糖引起的细胞内低糖血症的情况下，下丘脑和脑干水平观察到的 c-Fos/内脂素-1 共定位与胰岛素诱导的低血糖反应相似。此外，使用 Fluorogold 作为逆行示踪剂，我们发现低血糖激活的迷走神经节前 DMNX 神经元靶向胃和胰腺。总之，这些结果表明，内脂素能神经元的一个亚群属于低血糖激活的中枢网络，内脂素-1 参与了低血糖反应中观察到的生理和激素反调节的触发。
