Perspectives in diabetes - Neuronal glucosensing what do we know after 50 years?
Perspectives in diabetes - Neuronal glucosensing what do we know after 50 years?
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DOI：
10.2337/diabetes.53.10.2521
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发表时间：
2004-10-01
期刊：
影响因子：
7.7
通讯作者：
Dunn-Meynell, AA
中科院分区：
文献类型：
--
作者：
Levin, BE;Routh, VH;Dunn-Meynell, AA
葡萄糖敏感神经元是一种特殊的细胞，它使用葡萄糖作为信号分子来改变它们的动作电位频率，以响应环境葡萄糖水平的变化。葡萄糖激酶（GK）似乎是大多数神经元葡萄糖传感的主要调节因子，但几乎肯定存在其他调节因子。当葡萄糖水平升高时，葡萄糖兴奋的神经元增加其活性，并且大多数使用GK和ATP敏感的K+通道作为葡萄糖诱导的信号传导的最终效应器。葡萄糖抑制（GI）神经元在低葡萄糖水平下增加其活性。虽然许多人使用GK，但尚不清楚GI神经元葡萄糖感知的最终途径是什么。葡萄糖敏感神经元位于大脑部位，并响应和整合参与能量稳态调节和其他生物功能的各种激素、代谢、递质和肽信号。虽然目前还不确定血糖的每日波动是否在这些生理功能中发挥特定的调节作用，但很明显，葡萄糖可用性的大幅下降刺激食物摄入和反调节反应，恢复葡萄糖水平以维持脑功能。最后，在肥胖症和反复发作的低血糖症后，葡萄糖感知发生改变，这种改变的感知可能导致这些疾病的不良后果。因此，尽管我们已经知道了很多，但关于大脑葡萄糖传感神经元的生理功能还有很多需要了解。
Glucosensing neurons are specialized cells that use glucose as a signaling molecule to alter their action potential frequency in response to variations in ambient glucose levels. Glucokinase (GK) appears to be the primary regulator of most neuronal glucosensing, but other regulators almost certainly exist. Glucose-excited neurons increase their activity when glucose levels rise, and most use GK and an ATP-sensitive K+ channel as the ultimate effector of glucose-induced signaling. Glucose-inhibited (GI) neurons increase their activity at low glucose levels. Although many use GK, it is unclear what the final pathway of GI neuronal glucosensing is. Glucosensing neurons are located in brain sites and respond to and integrate a variety of hormonal, metabolic, transmitter, and peptide signals involved in the regulation of energy homeostasis and other biological functions. Although it is still uncertain whether daily fluctuations in blood glucose play a specific regulatory role in these physiological functions, it is clear that large decreases in glucose availability stimulate food intake and counterregulatory responses that restore glucose levels to sustain cerebral function. Finally, glucosensing is altered in obesity and after recurrent bouts of hypoglycemia, and this altered sensing may contribute to the adverse outcomes of these conditions. Thus, although much is known, much remains to be learned about the physiological function of brain glucosensing neurons.