Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism

dc.contributor.authorSepulveda-Quinenao, Claudia
dc.contributor.authorRodriguez, Juan M.
dc.contributor.authorDiaz-Castro, Francisco
dc.contributor.authordel Campo, Andrea
dc.contributor.authorBravo-Sagua, Roberto
dc.contributor.authorTroncoso, Rodrigo
dc.date.accessioned2025-01-20T21:06:49Z
dc.date.available2025-01-20T21:06:49Z
dc.date.issued2022
dc.description.abstractGlucocorticoids (GC) are steroids hormones that drive circulating glucose availability through gluconeogenesis in the liver. However, alternative splicing of the GR mRNA produces two isoforms, termed GR alpha and GR beta. GR alpha is the classic receptor that binds to GCs and mediates the most described actions of GCs. GR beta does not bind GCs and acts as a dominant-negative inhibitor of GR alpha. Moreover, GR beta has intrinsic and GR alpha-independent transcriptional activity. To date, it remains unknown if GR beta modulates glucose handling in hepatocytes. Therefore, the study aims to characterize the impact of GR beta overexpression on glucose uptake and storage using an in vitro hepatocyte model. Here we show that GR beta overexpression inhibits the induction of gluconeogenic genes by dexamethasone. Moreover, GR beta activates the Akt pathway, increases glucose transports mRNA, increasing glucose uptake and glycogen storage as an insulin-mimetic. Our results suggest that GR beta has agonist-independent insulin-mimetic actions in HepG2 cells.
dc.fuente.origenWOS
dc.identifier.doi10.3390/ijms23105582
dc.identifier.eissn1422-0067
dc.identifier.urihttps://doi.org/10.3390/ijms23105582
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93373
dc.identifier.wosidWOS:000803236900001
dc.issue.numero10
dc.language.isoen
dc.revistaInternational journal of molecular sciences
dc.rightsacceso restringido
dc.subjectglucocorticoid receptor beta
dc.subjectliver
dc.subjectglucose
dc.subjectinsulin
dc.subjectglycogen
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGlucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism
dc.typeartículo
dc.volumen23
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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