Objective. High glucose- (HG-) induced neuronal cell death is responsible for the development of diabetic neuropathy. However,\nthe effect of HG on metabolism in neuronal cells is still unclear. Materials and Methods.The neural-crest derived PC12 cells were\ncultured for 72 h in the HG (75mM) or control (25mM) groups.We used NMR-based metabolomics to examine both intracellular\nand extracellular metabolic changes in HG-treated PC12 cells. Results. We found that the reduction in intracellular lactate may\nbe due to excreting more lactate into the extracellular medium under HG condition. HG also induced the changes of other\nenergy-related metabolites, such as an increased succinate and creatine phosphate. Our results also reveal that the synthesis of\nglutamate from the branched-chain amino acids (isoleucine and valine)may be enhanced under HG. Increased levels of intracellular\nalanine, phenylalanine, myoinositol, and choline were observed in HG-treated PC12 cells. In addition, HG-induced decreases in\nintracellular dimethylamine, dimethylglycine, and 3-methylhistidine may indicate a downregulation of methyl group metabolism.\nConclusions. Our metabolomic results suggest that HG-induced neuronal cell death may be attributed to a series of metabolic\nchanges, involving energy metabolism, amino acids metabolism, osmoregulation and membrane metabolism, and methyl group\nmetabolism.
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