Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus
Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus
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DOI：
10.2337/diabetes.50.12.2673
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发表时间：
2001-12-01
期刊：
影响因子：
7.7
通讯作者：
Routh, VH
中科院分区：
文献类型：
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作者：
Song, ZT;Levin, BE;Routh, VH
在14- 21日龄雄性Sprague-Dawley大鼠脑片上，采用视觉引导切片-贴片记录技术研究了下丘脑腹内侧核（VMN）的葡萄糖感受神经元。当细胞外葡萄糖水平增加（从2.5至5或10 mmol/l）或降低（从2.5至0.1 mmol/l）时，进行全细胞电流钳记录。使用这些生理条件来定义葡萄糖传感神经元，两种亚型的VMN葡萄糖传感神经元直接响应于细胞外葡萄糖水平的改变。另外三种亚型本身不直接葡萄糖感应，而是通过细胞外葡萄糖的变化进行突触前调制。在VMN神经元中，14%的细胞外葡萄糖减少直接抑制（葡萄糖兴奋[GE]），3%的细胞外葡萄糖减少直接兴奋（葡萄糖抑制[GI]）。另外14%的突触前兴奋减少葡萄糖（PED神经元）。当细胞外葡萄糖升高到>2.5 mmol/l时，其他两种葡萄糖感受神经元亚型要么被突触前抑制（PIR; 11%），要么被兴奋（PER; 8%）。GE神经元通过ATP敏感性K+（K-ATP）通道感知葡萄糖减少。增加葡萄糖对PIR神经元的抑制作用似乎是由突触前γ-氨基丁酸能葡萄糖敏感神经元介导的，该神经元可能起源于VMN之外。最后，在饮食诱导的肥胖和2型糖尿病的啮齿动物模型中，所有类型的葡萄糖传感神经元的数量都较少，并且对葡萄糖表现出异常反应。
Glucosensing neurons in the ventromedial hypothalamic nucleus (VMN) were studied using visually guided slice-patch recording techniques in brain slices from 14- to 21-day-old male Sprague-Dawley rats. Whole-cell current-clamp recordings were made as extracellular glucose levels were increased (from 2.5 to 5 or 10 mmol/1) or decreased (from 2.5 to 0.1 mmol/1). Using these physiological conditions to define glucosensing neurons, two subtypes of VMN glucosensing neurons were directly responsive to alterations in extracellular glucose levels. Another three subtypes were not directly glucose-sensing themselves, but rather were presynaptically modulated by changes in extracellular glucose. Of the VMN neurons, 14% were directly inhibited by decreases in extracellular glucose (glucose-excited [GE]), and 3% were directly excited by decreases in extracellular glucose (glucose-inhibited [GI]). An additional 14% were presynaptically excited by decreased glucose (PED neurons). The other two subtypes of glucosensing neurons were either presynaptically inhibited (PIR; 11%) or excited (PER; 8%) when extracellular glucose was raised to >2.5 mmol/l. GE neurons sensed decreased glucose via an ATP-sensitive K+ (K-ATP) channel. The inhibitory effect of increased glucose on PIR neurons appears to be mediated by a presynaptic gamma -aminobutyric acid-ergic glucosensing neuron that probably originates outside the VMN. Finally, all types of glucosensing neurons were both fewer in number and showed abnormal responses to glucose in a rodent model of diet-induced obesity and type 2 diabetes.