Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle.
Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle.
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下丘脑腹内侧葡萄糖感应和葡萄糖稳态在整个动情周期中变化。
DOI：
10.1016/j.physbeh.2016.09.021
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发表时间：
2016
影响因子：
2.9
通讯作者：
Routh,VanessaH
中科院分区：
文献类型：
--
作者：
Santiago,AmmyM;Clegg,DeborahJ;Routh,VanessaH
17 β-雌二醇（17βE）部分通过中枢介导的机制调节葡萄糖稳态。在雌性啮齿动物中，卵巢周期对低血糖反调节和葡萄糖耐量的影响尚不清楚。我们以前发现，在青春期前的女性，17βE调节腹内侧核腹外侧部分（VL-VMN）内的非适应性葡萄糖抑制（GI）和适应性GI（AdGI）神经元的葡萄糖感知。非适应性GI神经元持续降低其活动，葡萄糖增加，而AdGI神经元短暂响应葡萄糖增加。为了开始了解动情周期中雌激素水平的内源性波动是否影响下丘脑葡萄糖感知和葡萄糖稳态，我们评估了动情周期各阶段的低血糖反调节和葡萄糖耐量是否不同。我们假设，在整个发情周期中，对胰岛素诱导的低血糖（IIH）和/或葡萄糖耐量的反应会根据17βE可用性的变化而变化。此外，这些变化将相关的葡萄糖敏感性的VL-VMN葡萄糖敏感神经元（GSNs）。MethodsThese假设进行了测试，在雌性小鼠通过测量响应IIH，葡萄糖耐量和葡萄糖敏感性的VL-VMN GSNs在每个阶段的发情周期。此外，将动情前期生理脑浓度的17βE急性应用于动情期间分离的脑切片，并测定VL-VMN GSN对低葡萄糖的反应。结果在动情期间，对IIH的反应最强。非适应性GI和AdGI神经元对葡萄糖从2.5 mM降低到0.5 mM的反应也在间情期达到峰值，这种作用被17βE所减弱。相反，葡萄糖（GE）兴奋的GSNs亚群的葡萄糖敏感性不受动情期或外源性17βE application.ConclusionThese数据表明，生理波动循环17βE水平在整个动情周期导致下丘脑葡萄糖感知和IIH的反应的变化。
Objective17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs).MethodsThese hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed.ResultsThe response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5 mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application.ConclusionThese data suggest that physiological fluctuations in circulating 17βE levels across the estrous cycle lead to changes in hypothalamic glucose sensing and the response to IIH.