Localization of glucokinase gene expression in the rat brain
Localization of glucokinase gene expression in the rat brain
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DOI：
10.2337/diabetes.49.5.693
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发表时间：
2000-05-01
期刊：
影响因子：
7.7
通讯作者：
Levin, BE
中科院分区：
文献类型：
--
作者：
Lynch, RM;Tompkins, LS;Levin, BE
大脑包含一群葡萄糖感受性神经元，它们会改变自己的放电率，以应对葡萄糖浓度的升高。在胰岛β细胞中，葡萄糖激酶(GK)是糖酵解中的限速酶，通过调节细胞内ATP的产生来调节葡萄糖诱导的胰岛素释放。GK的类似作用被认为是神经元葡萄糖感觉的基础。通过原位杂交，GR mRNA被定位于下丘脑中被认为含有较多葡萄糖感受性神经元的区域(弓状核、腹内侧核、背内侧核、室旁核和外侧区)。GK也存在于未发现糖感受性神经元的脑区(外侧缰核、终纹床核、下橄榄核、视交叉后区和视前内侧区，以及丘脑室旁后核、脚间核、动眼神经核和嗅前核团)。相反，在含有葡萄糖感受性神经元的孤束核或第三脑室的室管膜细胞中没有发现GK信息，其他人也描述了GK信息的存在。在弓状核，75%的神经肽Y阳性神经元也表达GK，大多数GK(+)神经元也表达KIR6.2(三磷酸腺苷敏感钾通道的造孔亚单位)，通过逆转录-聚合酶链式反应(RT-PCR)证实了GK mRNA在下丘脑微孔样本中的解剖分布。回收的PCR产物的核苷酸序列分析表明，与肝脏和β细胞GK的1092-1411核苷酸(在外显子9和10内)相同。GK mRNA在下丘脑已知含有葡萄糖敏感神经元的区域的特殊解剖定位，以及KIR6.2和NPY在GK(+)神经元中的共同表达，支持GK作为神经肽神经元中葡萄糖感觉的主要决定因素，整合了与外周能量代谢相关的多种信号。
The brain contains a subpopulation of glucosensing neurons that alter their firing rate in response to elevated glucose concentrations. In pancreatic beta-cells, glucokinase (GK), the rate-limiting enzyme in glycolysis, mediates glucose-induced insulin release by regulating intracellular ATP production. A similar role for GK is proposed to underlie neuronal glucosensing. Via in situ hybridization, GR mRNA was localized to hypothalamic areas that are thought to contain relatively large populations of glucosensing neurons (the arcuate, ventromedial, dorsomedial, and paraventricular nuclei and the lateral area). GK also was found in brain areas without known glucosensing neurons (the lateral habenula, the bed nucleus stria terminalis, the inferior olive, the retrochiasmatic and medial preoptic areas, and the thalamic posterior paraventricular, interpeduncular, oculomotor, and anterior olfactory nuclei). Conversely, GK message was not found in the nucleus tractus solitarius, which contains glucosensing neurons, or in ependymal cells lining the third ventricle, where others have described its presence. In the arcuate nucleus, >75% of neuropeptide Y-positive neurons also expressed GK, and most GK(+) neurons also expressed KIR6.2 (the pore-forming subunit of the ATP-sensitive K+ channel), The anatomic distribution of GK mRNA mas confirmed in micropunch samples of hypothalamus via reverse transcription-polymerase chain reaction (RT-PCR). Nucleotide sequencing of the recovered PCR product indicated identity with nucleotides 1092-1411 (within exon 9 and 10) of hepatic and beta-cell GK. The specific anatomic localization of GK mRNA in hypothalamic areas known to contain glucosensing neurons and the coexpression of KIR6.2 and NPY in GK(+) neurons support a role for GK as a primary determinant of glucosensing in neuropeptide neurons that integrate multiple signals relating to peripheral energy metabolism.