Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784715424186761216 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9141770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sepulvedaquinenaoclaudia glucocorticoidreceptorboverexpressionhasagonistindependentinsulinmimeticeffectsonhepg2glucosemetabolism AT rodriguezjuanm glucocorticoidreceptorboverexpressionhasagonistindependentinsulinmimeticeffectsonhepg2glucosemetabolism AT diazcastrofrancisco glucocorticoidreceptorboverexpressionhasagonistindependentinsulinmimeticeffectsonhepg2glucosemetabolism AT delcampoandrea glucocorticoidreceptorboverexpressionhasagonistindependentinsulinmimeticeffectsonhepg2glucosemetabolism AT bravosaguaroberto glucocorticoidreceptorboverexpressionhasagonistindependentinsulinmimeticeffectsonhepg2glucosemetabolism AT troncosorodrigo glucocorticoidreceptorboverexpressionhasagonistindependentinsulinmimeticeffectsonhepg2glucosemetabolism |