ArticleAmerican journal of physiology. Endocrinology and metabolism2013
6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in part via a mechanism dependent upon orphan nuclear receptor NR4A3.
Article in American journal of physiology. Endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Lysed erythrocyte membranes metabolically prime endothelial cells for angiogenesis.Angiogenesis · 2026Article
- Review
- Potential Roles of Nr4a3-Mediated Inflammation in Immunological and Neurological Diseases.Molecular neurobiology · 2024Review
- Neuregulin (NRG-1β) Is Pro-Myogenic and Anti-Cachectic in Respiratory Muscles of Post-Myocardial Infarcted Swine.Biology · 2022Article
- Molecular Characteristics of T Cell-Mediated Tumor Killing in Hepatocellular Carcinoma.Frontiers in immunology · 2022Article
- Nuclear Receptors in Energy Metabolism.Advances in experimental medicine and biology · 2022Article
- Effects of Exercise and a High-Fat, High-Sucrose Restriction Diet on Metabolic Indicators, Nr4a3, and Mitochondria-Associated Protein Expression in the Gastrocnemius Muscles of Mice with Diet-Induced Obesity.Journal of obesity & metabolic syndrome · 2021Article
- Severe recurrent nocturnal hypoglycemia during chemotherapy with 6-mercaptopurine in a child with acute lymphoblastic leukemia.Annals of pediatric endocrinology & metabolism · 2018Article
- Role of AMPK signalling pathway during compensatory growth in pigs.BMC genomics · 2018Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
The purine anti-metabolite 6-mercaptopurine (6-MP) is widely used for the treatment of leukemia and inflammatory diseases. The cellular effects of 6-MP on metabolism remain unknown; however, 6-MP was recently found to activate the orphan nuclear receptor NR4A3 in skeletal muscle cell lines. We have reported previously that NR4A3 (also known as NOR-1, MINOR) is a positive regulator of insulin sensitivity in adipocytes. To further explore the role of NR4A3 activation in insulin action, we explored whether 6-MP activation of NR4A3 could modulate glucose transport system activity in L6 skeletal muscle cells. We found that 6-MP increased both NR4A3 expression and NR4A3 transcriptional activity and enhanced glucose transport activity via increasing GLUT4 translocation in both basal and insulin-stimulated L6 cells in an NR4A3-dependent manner. Furthermore, 6-MP increased levels of phospho-AS160, although this effect was not modulated by NR4A3 overexpression or knockdown. These primary findings provide a novel proof of principle that 6-MP, a small molecule NR4A3 agonist, can augment glucose uptake in insulin target cells, although this occurs via both NR4A3-dependent and -independent actions; the latter is related to an increase in phospho-AS160. These results establish a novel target for development of new treatments for insulin resistance.
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