IN SITU COEXPRESSION OF GLUCOSE AND MONOCARBOXYLATE TRANSPORTER mRNAs IN METABOLIC-SENSITIVE CAUDAL DORSAL VAGAL COMPLEX CATECHOLAMINERGIC NEURONS: TRANSCRIPTIONAL REACTIVITY TO INSULIN-INDUCED HYPOGLYCEMIA AND CAUDAL HINDBRAIN GLUCOSE OR LACTATE REPLETION DURING INSULIN-INDUCED HYPOGLYCEMIA
IN SITU COEXPRESSION OF GLUCOSE AND MONOCARBOXYLATE TRANSPORTER mRNAs IN METABOLIC-SENSITIVE CAUDAL DORSAL VAGAL COMPLEX CATECHOLAMINERGIC NEURONS: TRANSCRIPTIONAL REACTIVITY TO INSULIN-INDUCED HYPOGLYCEMIA AND CAUDAL HINDBRAIN GLUCOSE OR LACTATE REPLETION DURING INSULIN-INDUCED HYPOGLYCEMIA
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DOI：
10.1016/j.neuroscience.2009.08.074
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发表时间：
2009-12-15
期刊：
影响因子：
3.3
通讯作者：
Vavaiya, K. V.
中科院分区：
文献类型：
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作者：
Briski, K. P.;Cherian, A. K.;Vavaiya, K. V.
迷走神经背侧复合体（DVC）中代谢感觉神经元的神经化学表型仍不清楚。这些研究利用单细胞定量实时RT-PCR，结合激光弹射显微切割，以解决DVC A2神经元表达基因编码的特征代谢转换器，如葡萄糖激酶（GCK）和能量依赖性钾通道，K（ATP）的假设。研究表明，无论是葡萄糖或乳酸改变突触放电的DVC化学感觉神经元，后者的燃料输送到尾部后脑放大胰岛素诱导的低血糖症（IIH），并提高神经元葡萄糖和单羧酸转运蛋白，GCK，和磺酰脲-1 mRNA的DVC。因此，我们研究了额外的前提下，IIH修改A2底物转运蛋白和代谢转导基因谱，这种转录反应可能会被逆转外源性乳酸和/或葡萄糖。个体酪氨酸羟化酶（TH）免疫反应（IR）A2神经元显微解剖后2小时注射胰岛素或生理盐水，和连续尾侧第四脑室（CV 4）输注乳酸，葡萄糖，或人工脑脊液从尾侧DVC。数据显示，IIH降低A2神经元中的MCT 2，但升高GLUT 3、GLUT 4、GCK和SUR-1转录物。通过CV 4输注乳酸盐或葡萄糖进一步降低胰岛素注射大鼠的血糖水平。乳酸盐加胰岛素逆转了MCT 2 mRNA的低血糖降低，并进一步增强了A2神经元中的GLUT 3转录，而胰岛素注射大鼠的葡萄糖输注进一步增加了GLUT 3和GCK基因谱。本研究结果表明，尾侧DVC A2神经元表达代谢传感的分子标记物，以及编码葡萄糖和单羧酸转运蛋白的基因。IIH降低A2 MCT 2，但升高GLUT 3和GLUT 4基因谱的证据表明，葡萄糖可能是低血糖期间这些细胞的主要能量来源，而乳酸摄取减少（单独或相对于葡萄糖摄取）可能是细胞水平全身性葡萄糖缺乏症的关键表现。单一燃料补充不正常的低血糖模式的葡萄糖转运蛋白，GCK，或SUR-1的mRNA表达在A2神经元的研究结果意味着，这两种能量底物的充足供应是代谢平衡所需的，以及细胞适应的流行燃料可能会增加细胞对葡萄糖特异性代谢产物或其他产品的依赖。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The neurochemical phenotype(s) of metabolic sensing neurons in the dorsal vagal complex (DVC) remains unclear. These studies utilized single-cell quantitative real-time RT-PCR, in conjunction with laser-catapult microdissection, to address the hypothesis that DVC A2 neurons express genes that encode the characterized metabolic transducers, e.g. glucokinase (GCK) and the energy-dependent potassium channel, K(ATP). Studies show that either glucose or lactate alters synaptic firing of DVC chemosensory neurons, and that delivery of the latter fuel into the caudal hindbrain amplifies insulin-induced hypoglycemia (IIH) and elevates neuronal glucose and monocarboxylate transporter, GCK, and sulfonylurea-1 mRNA in the DVC. We thus examined the additional premise that IIH modifies A2 substrate transporter and metabolic transducer gene profiles, and that such transcriptional responses may be reversed by exogenous lactate and/or glucose. Individual tyrosine hydroxylase (TH)-immunoreactive (-ir) A2 neurons were microdissected from the caudal DVC 2 h after injection of insulin or saline, and continuous caudal fourth ventricular (CV4) infusion of lactate, glucose, or artificial cerebrospinal fluid. The data show that IIH decreased MCT2, but elevated GLUT3, GLUT4, GCK, and SUR-1 transcripts in A2 neurons. Blood glucose levels in insulin-injected rats were further reduced by CV4 infusion of either lactate or glucose. Lactate plus insulin reversed hypoglycemic reductions in MCT2 mRNA and further augmented GLUT3 transcripts in A2 neurons, whereas glucose infusion in insulin-injected rats further increased GLUT3 and GCK gene profiles. The present results demonstrate that caudal DVC A2 neurons express molecular markers for metabolic sensing, and genes that encode glucose and monocarboxylate transporters. Evidence that IIH reduces A2 MCT2, but elevates GLUT3 and GLUT4 gene profiles suggests that glucose may be a primary energy source to these cells during hypoglycemia, while decreased lactate uptake, alone or relative to glucose uptake, may be a critical manifestation of systemic glucose deficiency at the cellular level. Findings that singular fuel repletion does not normalize hypoglycemic patterns of glucose transporter, GCK, or SUR-1 mRNA expression in A2 neurons imply that sufficient supply of both energy substrates is required for metabolic balance, and that cellular adaptation to the prevalence of either fuel may increase cellular dependence on glucose-specific metabolites or other products. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.