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

Glucocorticoids (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 GRα and GRβ. GRα is the classic receptor that binds to GCs and mediates the most described actions o...

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Veröffentlicht in:International journal of molecular sciences 2022-05, Vol.23 (10), p.5582
Hauptverfasser: Sepúlveda-Quiñenao, Claudia, Rodriguez, Juan M, Díaz-Castro, Francisco, Del Campo, Andrea, Bravo-Sagua, Roberto, Troncoso, Rodrigo
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Sprache:eng
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Zusammenfassung:Glucocorticoids (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 GRα and GRβ. GRα is the classic receptor that binds to GCs and mediates the most described actions of GCs. GRβ does not bind GCs and acts as a dominant-negative inhibitor of GRα. Moreover, GRβ has intrinsic and GRα-independent transcriptional activity. To date, it remains unknown if GRβ modulates glucose handling in hepatocytes. Therefore, the study aims to characterize the impact of GRβ overexpression on glucose uptake and storage using an in vitro hepatocyte model. Here we show that GRβ overexpression inhibits the induction of gluconeogenic genes by dexamethasone. Moreover, GRβ activates the Akt pathway, increases glucose transports mRNA, increasing glucose uptake and glycogen storage as an insulin-mimetic. Our results suggest that GRβ has agonist-independent insulin-mimetic actions in HepG2 cells.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23105582