Metabolism-independent sugar sensing in central orexin neurons.
Metabolism-independent sugar sensing in central orexin neurons.
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DOI：
10.2337/db08-0548
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发表时间：
2008-10
期刊：
影响因子：
7.7
通讯作者：
Burdakov D
中科院分区：
文献类型：
--
作者：
González JA;Jensen LT;Fugger L;Burdakov D
目的：下丘脑特殊神经元的葡萄糖感知对于正常的能量平衡是至关重要的。在许多葡萄糖激活的神经元中，葡萄糖代谢被认为是葡萄糖感知的关键步骤，但葡萄糖抑制的神经元是否遵循相同的策略尚不清楚。外侧下丘脑的食欲素/下丘脑泌素神经元广泛投射葡萄糖抑制细胞，对正常认知唤醒和进食行为至关重要。在这里，我们使用不同的糖，能量代谢产物和药理学工具来探索食欲素细胞的葡萄糖敏感策略。研究设计和方法-我们进行了膜片钳记录的电活动的个别食欲素神经元明确确定转基因表达的绿色荧光蛋白在小鼠脑片。结果-我们表明：1）2-脱氧葡萄糖，一种不可代谢的葡萄糖类似物，模拟葡萄糖的作用; 2）用乳酸增加细胞内能量燃料的产生不会重现葡萄糖反应; 3）食欲素细胞葡萄糖传感不受葡萄糖激酶抑制剂四氧嘧啶、d-葡萄糖胺和N-乙酰基-d-葡萄糖胺的影响;和4）食欲素葡萄糖传感器检测甘露糖、D-葡萄糖和2-脱氧葡萄糖，但不检测半乳糖、L-葡萄糖、α-甲基-D-葡萄糖苷或果糖。结论-我们的新数据表明，下丘脑外侧的行为关键神经回路包含葡萄糖检测器，显示出新的糖选择性，可以独立于葡萄糖代谢。
OBJECTIVE— Glucose sensing by specialized neurons of the hypothalamus is vital for normal energy balance. In many glucose-activated neurons, glucose metabolism is considered a critical step in glucose sensing, but whether glucose-inhibited neurons follow the same strategy is unclear. Orexin/hypocretin neurons of the lateral hypothalamus are widely projecting glucose-inhibited cells essential for normal cognitive arousal and feeding behavior. Here, we used different sugars, energy metabolites, and pharmacological tools to explore the glucose-sensing strategy of orexin cells. RESEARCH DESIGN AND METHODS— We carried out patch-clamp recordings of the electrical activity of individual orexin neurons unambiguously identified by transgenic expression of green fluorescent protein in mouse brain slices. RESULTS— We show that 1) 2-deoxyglucose, a nonmetabolizable glucose analog, mimics the effects of glucose; 2) increasing intracellular energy fuel production with lactate does not reproduce glucose responses; 3) orexin cell glucose sensing is unaffected by glucokinase inhibitors alloxan, d-glucosamine, and N-acetyl-d-glucosamine; and 4) orexin glucosensors detect mannose, d-glucose, and 2-deoxyglucose but not galactose, l-glucose, α-methyl-d-glucoside, or fructose. CONCLUSIONS— Our new data suggest that behaviorally critical neurocircuits of the lateral hypothalamus contain glucose detectors that exhibit novel sugar selectivity and can operate independently of glucose metabolism.
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影响因子：
64.5
作者：
Lin, L;Faraco, J;Mignot, E
通讯作者：
Mignot, E
影响因子：
5.5
作者：
DEAN, PM;MATTHEWS, EK;SAKAMOTO, Y
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SAKAMOTO, Y
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作者：
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作者：
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影响因子：
5.3
作者：
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通讯作者：
Verkhratsky, A