Sodium-coupled glucose cotransporters contribute to hypothalamic glucose sensing.
Sodium-coupled glucose cotransporters contribute to hypothalamic glucose sensing.
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DOI：
10.2337/db06-0531
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发表时间：
2006-12
期刊：
影响因子：
7.7
通讯作者：
Gribble FM
中科院分区：
文献类型：
--
作者：
O'Malley D;Reimann F;Simpson AK;Gribble FM
下丘脑内的专门神经元具有感知和响应环境葡萄糖浓度变化的能力。我们研究了葡萄糖触发活动的葡萄糖兴奋（GE）神经元的机制，使用原代培养的大鼠下丘脑神经元荧光钙成像监测。35%（738/2139）的神经元通过将葡萄糖从3 mM增加到15 mM而兴奋，但只有9%（6/64）的GE神经元被甲苯磺丁脲激活，这表明涉及KATP通道独立机制。α-甲基吡喃葡萄糖苷（αMDG，12 mM）是钠葡萄糖协同转运蛋白（SGLT）的不可代谢底物，在67%的GE神经元中模拟了高糖的作用，葡萄糖和α MDG触发的兴奋均被Na+清除或SGLT抑制剂根皮苷（100 nM）阻断。在存在0.5 mM葡萄糖和甲苯磺丁脲的情况下，3.5 mM αMDG也可触发反应，支持SGLT相关机制在低和高底物浓度下的作用。用RT-PCR方法检测培养神经元和成年大鼠下丘脑中SGLT 1、SGLT 3a、SGLT 3b的表达。我们的研究结果表明，SGLT在下丘脑GE神经元葡萄糖感知中的新作用。
Specialised neurons within the hypothalamus have the ability to sense and respond to changes in ambient glucose concentrations. We investigated the mechanisms underlying glucose-triggered activity in glucose-excited (GE) neurons, using primary cultures of rat hypothalamic neurons monitored by fluorescence calcium imaging. 35% (738/2139) of neurons were excited by increasing glucose from 3 to 15mM, but only 9% (6/64) of these GE neurons were activated by tolbutamide, suggesting the involvement of a KATP channel-independent mechanism. α-Methylglucopyranoside (αMDG, 12mM), a non-metabolisable substrate of sodium glucose co-transporters (SGLTs), mimicked the effect of high glucose in 67% of GE neurons, and both glucose and αMDG-triggered excitation were blocked by Na+ removal or by the SGLT inhibitor, phloridzin (100nM). In the presence of 0.5mM glucose and tolbutamide, responses could also be triggered by 3.5mM αMDG, supporting a role for an SGLT-associated mechanism at low as well as high substrate concentrations. By RT-PCR, we detected SGLT1, SGLT3a, SGLT3b in both cultured neurons and adult rat hypothalamus. Our findings suggest a novel role for SGLTs in glucose-sensing by hypothalamic GE neurons.
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影响因子：
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