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

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 1H 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.

Keywords: 1H NMR; Astrocytes; Central neural system; High glucose; Metabonomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology*
  • Glucose / pharmacology*
  • Lactic Acid / metabolism*
  • Metabolomics
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Amino Acids
  • Lactic Acid
  • Glucose