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Volume 49 Issue 4
Apr.  2022
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Article Navigation >  Journal of Genetics and Genomics  > 2022  >  49(4): 299-307

The mechanisms of nucleotide actions in insulin resistance

doi: 10.1016/j.jgg.2022.01.006
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    a Metabolic Disease Research Center, Zhengzhou University Affiliated Zhengzhou Central Hospital, Zhengzhou, Henan 450007, China;

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    b Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China;

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    c Center for Advanced Medicine, College of Medicine, Zhengzhou University, Zhengzhou, Henan 450007, China;

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    d Department of Orthopedics, Zhengzhou Central Hospital, Zhengzhou, Henan 450000, China

Funds:

This study was supported by the starting funds from the Metabolic Disease Research Center, Zhengzhou University Affiliated Zhengzhou Central Hospital and the Center for Advanced Medicine, College of Medicine, Zhengzhou University, Zhengzhou to Jianping Ye.

  • Received Date: 2021-11-03
  • Accepted Date: 2022-01-24
  • Rev Recd Date: 2022-01-23
  • Publish Date: 2022-04-30
    Abstract
  • Insulin resistance contributes to metabolic disorders in obesity and type 2 diabetes. In mechanisms of insulin resistance, the roles of glucose, fatty acids, and amino acids have been extensively documented in literature. However, the activities of nucleotides remain to be reviewed comprehensively in the regulation of insulin sensitivity. Nucleotides are well known for their activities in biosynthesis of DNA and RNA as well as their signaling activities in the form of cAMP and cGAMP. Their activities in insulin resistance are dependent on the derivatives and corresponding receptors. ATP and NADH, derivatives of adenosine, inhibit insulin signaling inside cells by downregulation of activities of AMPK and SIRT1, respectively. ATP, ADP and AMP, the well-known energy carriers, regulate cellular responses to insulin outside cells through the purinergic receptors in cell surface. Current evidence suggests that ATP, NADH, cGAMP, and uridine are potential biomarkers of insulin resistance. However, GTP and cGMP are likely the markers of insulin sensitization. Here, studies crossing the biomedical fields are reviewed to characterize nucleotide activities in the regulation of insulin sensitivity. The knowledge brings new insights into the mechanisms of insulin resistance.
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      沈阳化工大学材料科学与工程学院 沈阳 110142

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