The mechanisms of nucleotide actions in insulin resistance |
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| Affiliation: | 1. Metabolic Disease Research Center, Zhengzhou University Affiliated Zhengzhou Central Hospital, Zhengzhou, Henan 450007, China;2. Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China;3. Center for Advanced Medicine, College of Medicine, Zhengzhou University, Zhengzhou, Henan 450007, China;4. Department of Orthopedics, Zhengzhou Central Hospital, Zhengzhou, Henan 450000, China;1. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;2. University of Chinese Academy of Sciences, Shijingshan District, Beijing 100049, China;3. CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China;4. Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK;5. CAS Center of Excellence for Animal Evolution and Genetics, Kunming, Yunnan 650223, China |
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| 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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| Keywords: | Insulin resistance Nucleotide Adenosine Guanosine Uridine AMPK Purinergic receptors |
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