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    GPR21 Inhibition Increases Glucose-Uptake in HepG2 Cells

    Kinsella, Gemma K. and Cannito, Stefania and Bordano, Valentina and Stephens, John C. and Rosa, Arianna C. and Miglio, Gianluca and Guaschino, Valeria and Iannaccone, Valeria and Findlay, John B.C. and Benetti, Elisa (2021) GPR21 Inhibition Increases Glucose-Uptake in HepG2 Cells. International Journal of Molecular Sciences, 22 (19). p. 10784. ISSN 1422-0067

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    GPR21 is a constitutively active, orphan, G-protein-coupled receptor, with in vivo studies suggesting its involvement in the modulation of insulin sensitivity. However, its precise contribution is not fully understood. As the liver is both a major target of insulin signalling and critically involved in glucose metabolism, the aim of this study was to examine the role of GPR21 in the regulation of glucose uptake and production in human hepatocytes. In particular, HepG2 cells, which express GPR21, were adopted as cellular models. Compared with untreated cells, a significant increase in glucose uptake was measured in cells treated with siRNA to downregulate GPR21 expression or with the GPR21-inverse agonist, GRA2. Consistently, a significantly higher membrane translocation of GLUT-2 was measured under these conditions. These effects were accompanied by an increased ratio of phAKT(Ser473)/tot-AKT and phGSK-3β(Ser9)/tot-GSK-3β, thus indicating a marked activation of the insulin signalling pathway. Moreover, a significant reduction in ERK activation was observed with GPR21 inhibition. Collectively, these results indicate that GPR21 mediates the negative effects on glucose uptake by the liver cells. In addition, they suggest that the pharmacological inhibition of GPR21 could be a novel strategy to improve glucose homeostasis and counteract hepatic insulin resistance.

    Item Type: Article
    Additional Information: Kinsella, G.K.; Cannito, S.; Bordano, V.; Stephens, J.C.; Rosa, A.C.; Miglio, G.; Guaschino, V.; Iannaccone, V.; Findlay, J.B.C.; Benetti, E. GPR21 Inhibition Increases Glucose-Uptake in HepG2 Cells. Int. J. Mol. Sci. 2021, 22, 10784.
    Keywords: GPR21; GPCRs; hepatocytes; hepatic insulin resistance;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17460
    Identification Number:
    Depositing User: Dr John Stephens
    Date Deposited: 24 Aug 2023 09:08
    Journal or Publication Title: International Journal of Molecular Sciences
    Refereed: Yes
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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