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Metabolomics and correlation network analyses of core biomarkers in type 2 diabetes

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Abstract

The identification of metabolic pathways and the core metabolites provide novel molecular targets for the prevention and treatment of diseases. Diabetes is often accompanied with multiple metabolic disorders including hyperglycemia and dyslipidemia. Analysis of the variances of plasma metabolites is critical for identifying potential therapeutic targets for diabetes. In the current study, non-diabetic subjects with normal glucose tolerance and diabetics (age 40–60 years; n = 42 per group) were selected and plasma samples were analyzed by GC–MS for various metabolites profiling followed by network analysis. Our study identified 24 differential metabolites that were mainly enriched in protein synthesis, lipid and amino acid metabolism. Furthermore, we applied the correlation network analysis on these differential metabolites in fatty acid and amino acid metabolism and identified glycerol, alanine and serine as the hub metabolites in diabetic group. In addition, we measured the activities of enzymes in gluconeogenesis and amino acid metabolism and found significant higher activities of fructose 1,6-bisphosphatase, pyruvate carboxylase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in diabetic patients. In contrast, the enzyme activities of glycolysis pathway (e.g., hexokinase, phosphofructokinase and pyruvate kinase) and TCA cycle (e.g., isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase and malate dehydrogenase) were reduced in diabetes. Together, our studies showed that the linoleic acid and amino acid metabolism were the most affected metabolic pathways and glycerol, alanine and serine could play critical role in diabetes. The integration of network analysis and metabolic data could provide novel molecular targets or biomarkers for diabetes.

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Funding

This study was supported by National Natural Science Foundation of China (NSFC) (Grant nos. 81570655, 81770728).

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Authors and Affiliations

  1. The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, China

    Wenjuan Lin, Meng Chen, Xuewei Zheng, Di Gao, Zhe Yang & Zhongmin Tian

  2. School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072, China

    Wenjuan Lin

  3. Department of Equipment, Shaanxi Second Provincial People’s Hospital, Xi’an, 710005, China

    Meng Wang

  4. Xi’an Gao Xin No. 1 High School, Xi’an, 710061, China

    Yutong Wu

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  1. Wenjuan Lin
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  2. Meng Wang
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  3. Meng Chen
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  4. Xuewei Zheng
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  5. Yutong Wu
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Correspondence to Zhe Yang or Zhongmin Tian.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by Xi’an Jiaotong University (Xjtu (2017)/2).

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Lin, W., Wang, M., Chen, M. et al. Metabolomics and correlation network analyses of core biomarkers in type 2 diabetes. Amino Acids 52, 1307–1317 (2020). https://doi.org/10.1007/s00726-020-02891-8

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