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

International Journal of Molecular Sciences

卷:23

Roberto Bravo-Sagua¹  Andrea del Campo²  Francisco Díaz-Castro³  Rodrigo Troncoso³  Juan M. Rodriguez³  Claudia Sepúlveda-Quiñenao³ 

[1]Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago 8380492, Chile

[2]|Laboratorio de Fisiología y Bioenergética Celular, Escuela de Química y Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile

[3]|Laboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago 7830490, Chile

关键词: glucocorticoid receptor β;    liver;    glucose;    insulin;    glycogen;   

DOI  :  10.3390/ijms23105582

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown