Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons.
Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons.
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DOI：
10.1016/j.molmet.2016.08.002
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发表时间：
2016-10
影响因子：
8.1
通讯作者：
Routh VH
中科院分区：
文献类型：
--
作者：
Santiago AM;Clegg DJ;Routh VH
大脑对葡萄糖稳态的调节是性别二态的；然而，性激素对新陈代谢敏感的大脑区域下丘脑腹内侧核(VMN)内特定神经元群体的影响尚未完全确定。葡萄糖兴奋(GE)和葡萄糖抑制(GI)神经元分布于整个VMN，可能在血糖和能量平衡中起关键作用。在VMN的腹外侧部(VL-VMN)，葡萄糖感觉神经元和雌激素受体(ER)分布重叠。因此，我们验证了VL-VMN葡萄糖感觉神经元是性二态的假设，并受到17β-雌二醇(17βE)的调节。在17βE存在和不存在的情况下，对年龄和体重匹配的雌性和雄性小鼠脑片进行了VL-VMN葡萄糖敏感神经元的电生理记录。我们发现了一类新的VL-VMN GI神经元，它们对低糖的反应是短暂的，尽管持续暴露在低糖中。到目前为止，我们将这些新发现的VL-VMN GI神经元称为适应神经元或AdGI神经元。我们发现了对低糖的性二型性反应，雄性不适应的GI神经元，而不是AdGI神经元，对低糖的反应比女性更强烈。17βE通过激活雌激素受体β和抑制AMP激活的激酶，减弱非适应性Gi和AdGi神经元对低糖的反应。相反，17βE对GE或非葡萄糖感受性神经元均无影响。这些数据提示，下丘脑VMN葡萄糖感觉的性别差异和雌激素调节可能有助于葡萄糖稳态的性别二型性。下丘脑对葡萄糖的敏感度是性二态的。17βE拮抗低糖状态下葡萄糖抑制神经元的激活。雌激素对葡萄糖感觉的调节可能介导性二态在葡萄糖稳态中的作用。
Brain regulation of glucose homeostasis is sexually dimorphic; however, the impact sex hormones have on specific neuronal populations within the ventromedial hypothalamic nucleus (VMN), a metabolically sensitive brain region, has yet to be fully characterized. Glucose-excited (GE) and -inhibited (GI) neurons are located throughout the VMN and may play a critical role in glucose and energy homeostasis. Within the ventrolateral portion of the VMN (VL-VMN), glucose sensing neurons and estrogen receptor (ER) distributions overlap. We therefore tested the hypothesis that VL-VMN glucose sensing neurons were sexually dimorphic and regulated by 17β-estradiol (17βE). Electrophysiological recordings of VL-VMN glucose sensing neurons in brain slices isolated from age- and weight-matched female and male mice were performed in the presence and absence of 17βE. We found a new class of VL-VMN GI neurons whose response to low glucose was transient despite continued exposure to low glucose. Heretofore, we refer to these newly identified VL-VMN GI neurons as ‘adapting’ or AdGI neurons. We found a sexual dimorphic response to low glucose, with male nonadapting GI neurons, but not AdGI neurons, responding more robustly to low glucose than those from females. 17βE blunted the response of both nonadapting GI and AdGI neurons to low glucose in both males and females, which was mediated by activation of estrogen receptor β and inhibition of AMP-activated kinase. In contrast, 17βE had no impact on GE or non-glucose sensing neurons in either sex. These data suggest sex differences and estrogenic regulation of VMN hypothalamic glucose sensing may contribute to the sexual dimorphism in glucose homeostasis. Hypothalamic glucose sensitivity is sexually dimorphic. 17βE blunts activation of glucose inhibited neurons in low glucose. Estrogen regulation of glucose sensing may mediate sexual dimorphisms in glucose homeostasis.
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影响因子：
--
作者：
Gustavsson C;Yassin K;Wahlström E;Cheung L;Lindberg J;Brismar K;Ostenson CG;Norstedt G;Tollet-Egnell P
通讯作者：
Tollet-Egnell P
影响因子：
8.2
作者：
AMIEL, SA;MARAN, A;MACDONALD, IA
通讯作者：
MACDONALD, IA
影响因子：
8.2
作者：
Bryzgalova, G;Gao, H;Khan, A
通讯作者：
Khan, A
影响因子：
9.8
作者：
DIAMOND, MP;JONES, T;SHERWIN, RS
通讯作者：
SHERWIN, RS
影响因子：
5.3
作者：
Burdakov, D;Gerasimenko, O;Verkhratsky, A
通讯作者：
Verkhratsky, A