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高糖环境下培养的星形胶质细胞中乳酸生成和氨基酸利用的时间依赖性。

Time-Dependent Lactate Production and Amino Acid Utilization in Cultured Astrocytes Under High Glucose Exposure.

机构信息

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

出版信息

Mol Neurobiol. 2018 Feb;55(2):1112-1122. doi: 10.1007/s12035-016-0360-y. Epub 2017 Jan 16.

Abstract

Accumulating investigations have focused on the severity of central nervous system (CNS) complications in diabetic patients. The effects of the high glucose (HG) probably attribute to the metabolic disturbances in CNS. Astrocytes, with powerful ability of metabolic regulation, play crucial roles in physiological and pathological processes in CNS. Hence, an in-depth analysis as to metabolic alterations of astrocytes exposure to HG would facilitate to explore the underlying pathogenesis. In this study, the H NMR-based metabonomic approach was performed to characterize the metabolic variations of intracellular metabolites and corresponding culture media in a time-dependent manner. Our results revealed a significant elevation in lactate production and release. Four amino acids, leucine, isoleucine, methionine and tyrosine, were the most important metabolites for utilization. Also, profound disturbances of several metabolic pathways, including osmoregulation, energy metabolism, and cellular biosynthesis were observed. In that sense, the detailed information of astrocyte metabolism under HG exposure provides us a comprehensive understanding of the intrinsic metabolic disorders in CNS during hyperglycemia or diabetes.

摘要

越来越多的研究集中在糖尿病患者中枢神经系统(CNS)并发症的严重性上。高血糖(HG)的影响可能归因于 CNS 的代谢紊乱。星形胶质细胞具有强大的代谢调节能力,在 CNS 的生理和病理过程中发挥着关键作用。因此,深入分析星形胶质细胞暴露于 HG 时的代谢变化将有助于探索潜在的发病机制。在这项研究中,我们采用基于 1H-NMR 的代谢组学方法,以时间依赖性的方式描述细胞内代谢物和相应培养基的代谢变化。我们的结果表明,乳酸的产生和释放显著增加。亮氨酸、异亮氨酸、蛋氨酸和酪氨酸这四种氨基酸是最重要的利用代谢物。此外,还观察到包括渗透压调节、能量代谢和细胞生物合成在内的几个代谢途径的深刻紊乱。从这个意义上说,HG 暴露下星形胶质细胞代谢的详细信息为我们提供了对高血糖或糖尿病期间 CNS 内在代谢紊乱的全面理解。

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