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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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Autores principales: Sepúlveda-Quiñenao, Claudia, Rodriguez, Juan M., Díaz-Castro, Francisco, del Campo, Andrea, Bravo-Sagua, Roberto, Troncoso, Rodrigo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141770/
https://www.ncbi.nlm.nih.gov/pubmed/35628392
http://dx.doi.org/10.3390/ijms23105582
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author Sepúlveda-Quiñenao, Claudia
Rodriguez, Juan M.
Díaz-Castro, Francisco
del Campo, Andrea
Bravo-Sagua, Roberto
Troncoso, Rodrigo
author_facet Sepúlveda-Quiñenao, Claudia
Rodriguez, Juan M.
Díaz-Castro, Francisco
del Campo, Andrea
Bravo-Sagua, Roberto
Troncoso, Rodrigo
author_sort Sepúlveda-Quiñenao, Claudia
collection PubMed
description 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.
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spelling pubmed-91417702022-05-28 Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism Sepúlveda-Quiñenao, Claudia Rodriguez, Juan M. Díaz-Castro, Francisco del Campo, Andrea Bravo-Sagua, Roberto Troncoso, Rodrigo Int J Mol Sci Brief Report 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. MDPI 2022-05-17 /pmc/articles/PMC9141770/ /pubmed/35628392 http://dx.doi.org/10.3390/ijms23105582 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Sepúlveda-Quiñenao, Claudia
Rodriguez, Juan M.
Díaz-Castro, Francisco
del Campo, Andrea
Bravo-Sagua, Roberto
Troncoso, Rodrigo
Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism
title Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism
title_full Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism
title_fullStr Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism
title_full_unstemmed Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism
title_short Glucocorticoid Receptor β Overexpression Has Agonist-Independent Insulin-Mimetic Effects on HepG2 Glucose Metabolism
title_sort glucocorticoid receptor β overexpression has agonist-independent insulin-mimetic effects on hepg2 glucose metabolism
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141770/
https://www.ncbi.nlm.nih.gov/pubmed/35628392
http://dx.doi.org/10.3390/ijms23105582
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