Glucocorticoid receptor β overexpression has agonist-independent insulin-mimetic effects on HepG2 glucose metabolism
2022
Sepúlveda Quiñenao, Claudia Patricia | Rodríguez Silva, José Manuel | Díaz Castro, Francisco | Campo, Andrea del | Bravo Sagua, Roberto Francisco | Troncoso Cotal, Rodrigo Hernán
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 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.
Show more [+] Less [-]Agencia Nacional de Investigacion y Desarrollo (ANID), Chile: FONDAP 15130011 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1191078 11190756 11201267 Universidad de Chile, Chile ABCvital 02-2018 U Inicia UI-006/19 PAI 77170004-2017
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