GPR21 Inhibition Increases Glucose-Uptake in HepG2 Cells
| Autor: | Valeria Guaschino, Valentina Bordano, Stefania Cannito, Gianluca Miglio, Elisa Benetti, John C. Stephens, Valeria Iannaccone, John B. C. Findlay, Gemma K. Kinsella, Arianna Carolina Rosa |
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| Přispěvatelé: | Progetto di Ateneo/CSP 2016- CSTO161899 cod. S1618 L1 BENE02 |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
GPCRs GPR21 Hepatic insulin resistance Hepatocytes Glucose Hep G2 Cells medicine.medical_specialty QH301-705.5 Glucose uptake hepatic insulin resistance Carbohydrate metabolism Catalysis Article Receptors G-Protein-Coupled Inorganic Chemistry Insulin resistance Downregulation and upregulation In vivo Internal medicine medicine Glucose homeostasis Humans Insulin Physical and Theoretical Chemistry Biology (General) Receptor Molecular Biology QD1-999 Spectroscopy Chemistry Organic Chemistry General Medicine medicine.disease Computer Science Applications Endocrinology hepatocytes Insulin Resistance Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 19 International Journal of Molecular Sciences, Vol 22, Iss 10784, p 10784 (2021) Articles |
| ISSN: | 1422-0067 1661-6596 |
| DOI: | 10.3390/ijms221910784 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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