Glucosensing neurons do more than just sense glucose
Glucosensing neurons do more than just sense glucose
复制标题
DOI：
10.1038/sj.ijo.0801916
复制
发表时间：
2001-12-01
影响因子：
4.9
通讯作者：
Levin, BE
中科院分区：
文献类型：
--
作者：
Levin, BE
大脑通过平衡能量摄入、消耗和储存来调节能量的动态平衡。为了做到这一点，它进化出了专门的神经元，接收和整合传递有关身体能量状态信息的传入神经和代谢信号。这些感应器-整合器-效应器神经元位于参与内稳态功能的大脑区域，如下丘脑、蓝斑、基底节、边缘系统和孤束核。感知和调节葡萄糖代谢的能力是至关重要的，因为葡萄糖是神经功能的首要代谢底物。大多数神经元使用葡萄糖作为能量底物，但葡萄糖敏感神经元也使用葡萄糖作为信号分子来调节神经元的放电和递质释放。有两种类型的葡萄糖感受性神经元，随着大脑葡萄糖水平的升高，它们的放电率要么增加(葡萄糖响应性，GR)，要么降低(葡萄糖敏感，GS)。人们对GS神经元感知葡萄糖的机制知之甚少。然而，GR神经元的功能似乎很像胰腺β细胞，在那里糖酵解调节ATP敏感的K+(K-ATP)通道的活动。K-ATP通道由四个成孔单元(Kir6.2)和四个磺酰基脲结合位点(SUR)组成。葡萄糖激酶(GK)似乎通过其在ATP糖酵解产生中的守门人作用来调节K-ATP通道的活性。因此，GK可作为GR神经元的标志物。下丘脑弓状核内的神经肽Y(NPY)和阿片黑素皮质素原(POMC)神经元是脑内能量稳态通路的重要组成部分。两者都表达Kir6.2和GK，以及瘦素受体。它们也接受内脏神经和内源性神经肽和递质的输入。这些与代谢相关的信号可以聚集在K-ATP通道的活性上，进而改变膜电位、神经元放电速率和肽/递质的释放。这些神经元的输出是调节能量平衡的效应器系统的组成部分。因此，弓状NPY和POMC神经元可能是这类重要的感觉-整合器-效应器神经元的原型。
The brain regulates energy homeostasis by balancing energy intake, expenditure and storage. To accomplish this, it has evolved specialized neurons that receive and integrate afferent neural and metabolic signals conveying information about the energy status of the body. These sensor-integrator-effector neurons are located in brain areas involved in homeostatic functions such as the hypothalamus, locus coeruleus basal ganglia, limbic system and nucleus tractus solitarius. The ability to sense and regulate glucose metabolism is critical because of glucose's primacy as a metabolic substrate for neural function. Most neurons use glucose as an energy substrate, but glucosensing neurons also use glucose as a signaling molecule to regulate neuronal firing and transmitter release. There are two types of glucosensing neurons that either increase (glucose responsive, GR) or decrease (glucose sensitive, GS) their firing rate as brain glucose levels rise. Little is known about the mechanism by which GS neurons sense glucose. However, GR neurons appear to function much like the pancreatic beta-cell where glycolysis regulates the activity of an ATP-sensitive K+ (K-ATP) channel. The K-ATP channel is composed of four pore-forming units (Kir6.2) and four sulfonylurea binding sites (SUR). Glucokinase (GK) appears to modulate K-ATP channel activity via its gatekeeper role in the glycolytic production of ATP. Thus, GK may serve as a marker for GR neurons. Neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus are critical components of the energy homeostasis pathways in the brain. Both express Kir6.2 and GK, as well as leptin receptors. They also receive visceral neural and intrinsic neuropeptide and transmitter inputs. Such metabolism-related signals can summate upon K-ATP channel activity which then alters membrane potential, neuronal firing rate and peptide/transmitter release. The outputs of these neurons are integral components of effector systems which regulate energy homeostasis. Thus, arcuate NPY and POMC neurons are probably prototypes of this important class of sensor-integrator-effector neurons.