The mechanisms of nucleotide actions in insulin resistance

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 i...

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Bibliographic Details
Published in:Journal of genetics and genomics 2022-04, Vol.49 (4), p.299-307
Main Authors: Liu, Kunpeng, Jin, Xiaogao, Zhang, Xiaoying, Lian, Hongkai, Ye, Jianping
Format: Article
Language:English
Subjects:
Adenosine
Adenosine Triphosphate
AMPK
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Guanosine
Humans
Insulin
Insulin resistance
Insulin Resistance - genetics
NAD
Nucleotide
Nucleotides
Purinergic receptors
Uridine
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Summary: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.
ISSN:1673-8527
DOI:10.1016/j.jgg.2022.01.006