Hypoglycemia activates orexin neurons and selectively increases hypothalamic orexin-B levels - Responses inhibited by feeding and possibly mediated by the nucleus of the solitary tract
Hypoglycemia activates orexin neurons and selectively increases hypothalamic orexin-B levels - Responses inhibited by feeding and possibly mediated by the nucleus of the solitary tract
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DOI：
10.2337/diabetes.50.1.105
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发表时间：
2001-01-01
期刊：
影响因子：
7.7
通讯作者：
Williams, G
中科院分区：
文献类型：
--
作者：
Cai, XJ;Evans, ML;Williams, G
食欲素是在下丘脑外侧区（LHA）表达的新型促食欲肽，在禁食大鼠中，低血糖会刺激其表达。我们利用即刻早期基因产物Fos研究了胰岛素诱导的低血糖过程中食欲素及其他神经元的激活情况。胰岛素（50 U/kg）在5小时后使血浆葡萄糖降低>50%，与注射生理盐水的对照组相比，进食量增加了6倍。允许进食的低血糖大鼠和血糖正常的对照组在LHA、室旁核（PVN）和弓状核（ARC）中均显示出少量Fos阳性（Fos(+)）神经元，在孤束核（NTS）中未显示出Fos阳性神经元，孤束核将内脏进食信号传递给LHA。在LHA中，进食的低血糖组和对照组中Fos(+)神经元总数相当（60 ± 6对52 ± 4个细胞/mm²，P>0.05），对食欲素呈免疫反应的Fos(+)神经元也是如此（1.4 ± 0.4对0.6 ± 0.4个细胞/mm²，P>0.05）。相比之下，禁食的低血糖大鼠在LHA中显示出明显更多的Fos(+)细胞核（96 ± 10个细胞/mm²，与其他两组相比P<0.05）以及Fos +食欲素神经元（8.4 ± 3.3个细胞/mm²，与其他两组相比P<0.001）。与进食的低血糖大鼠和对照组相比，它们在PVN和ARC中也显示出多2 - 3倍的Fos(+)细胞核（P<0.001），并且在NTS和迷走神经背核中显示出大量的Fos(+)神经元。在平行研究中，无论是禁食还是自由进食的低血糖大鼠，整个下丘脑的食欲素 - A水平均未改变，而禁食的低血糖大鼠中食欲素 - B水平比对照组和进食的低血糖组高10倍。这些数据支持我们的假设，即食欲素神经元受血糖水平下降的刺激，但容易被与营养摄入相关的信号抑制，并表明它们可能在功能上与NTS中的神经元活动相关联。食欲素 - A和 - B可能在低血糖的行为或神经内分泌反应中发挥特定作用。
Orexins are novel appetite-stimulating peptides expressed in the lateral hypothalamic area (LHA), and their expression is stimulated by hypoglycemia in fasted rats. We investigated activation of orexin and other neurons during insulin-induced hypoglycemia using the immediate early gene product Fos. Insulin (50 U/kg) lowered plasma glucose by >50% after 5 h and stimulated feeding sixfold compared with saline-injected controls. Hypoglycemic rats allowed to feed and normoglycemic controls both showed sparse Fos-positive (Fos(+)) neurons in the LHA and the paraventricular nucleus (PVN) and arcuate nucleus (ARC) and showed none in the nucleus of the solitary tract (NTS), which relays visceral feeding signals to the LHA. In the LHA, total numbers of Fos(+) neurons were comparable in fed hypoglycemic and control groups (60 +/- 6 vs. 52 +/- 4 cells/mm(2), P > 0.05), as were Fos(+) neurons immunoreactive for orexin (1.4 +/- 0.4 vs. 0.6 +/- 0.4 cells/mm(2), P > 0.05). By contrast, hypoglycemic rats that were fasted showed significantly more Fos(+) nuclei in the LHA (96 +/- 10 cells/mm(2), P < 0.05, vs. both other groups) and Fos+ orexin neurons (8.4 +/- 3.3 cells/mm(2), P < 0.001, vs. both other groups). They also showed two- to threefold more Fos(+) nuclei (P < 0.001) in the PVN and ARC than both fed hypoglycemic rats and controls and showed strikingly abundant Fos(+) neurons in the NTS and dorsal motor nucleus of the vagus. In parallel studies, whole hypothalamic orexin-A levels were not changed in hypoglycemic rats, whether fasted or freely fed, whereas orexin-B levels were 10-fold higher in hypoglycemic fasted rats than in control and hypoglycemic fed groups. These data support our hypothesis that orexin neurons are stimulated by falling glucose levels but are readily inhibited by signals related to nutrient ingestion and suggest that they may functionally link with neuronal activity in the NTS. Orexin-A and -B may play specific roles in behavioral or neuroendocrine responses to hypoglycemia.