Cargando…

CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity

Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition dec...

Descripción completa

Detalles Bibliográficos
Autores principales: Borgo, Christian, Milan, Gabriella, Favaretto, Francesca, Stasi, Fabio, Fabris, Roberto, Salizzato, Valentina, Cesaro, Luca, Belligoli, Anna, Sanna, Marta, Foletto, Mirto, Prevedello, Luca, Vindigni, Vincenzo, Bardini, Romeo, Donella-Deana, Arianna, Vettor, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730587/
https://www.ncbi.nlm.nih.gov/pubmed/29242563
http://dx.doi.org/10.1038/s41598-017-17809-w
_version_ 1783286371602923520
author Borgo, Christian
Milan, Gabriella
Favaretto, Francesca
Stasi, Fabio
Fabris, Roberto
Salizzato, Valentina
Cesaro, Luca
Belligoli, Anna
Sanna, Marta
Foletto, Mirto
Prevedello, Luca
Vindigni, Vincenzo
Bardini, Romeo
Donella-Deana, Arianna
Vettor, Roberto
author_facet Borgo, Christian
Milan, Gabriella
Favaretto, Francesca
Stasi, Fabio
Fabris, Roberto
Salizzato, Valentina
Cesaro, Luca
Belligoli, Anna
Sanna, Marta
Foletto, Mirto
Prevedello, Luca
Vindigni, Vincenzo
Bardini, Romeo
Donella-Deana, Arianna
Vettor, Roberto
author_sort Borgo, Christian
collection PubMed
description Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity.
format Online
Article
Text
id pubmed-5730587
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-57305872017-12-18 CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity Borgo, Christian Milan, Gabriella Favaretto, Francesca Stasi, Fabio Fabris, Roberto Salizzato, Valentina Cesaro, Luca Belligoli, Anna Sanna, Marta Foletto, Mirto Prevedello, Luca Vindigni, Vincenzo Bardini, Romeo Donella-Deana, Arianna Vettor, Roberto Sci Rep Article Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity. Nature Publishing Group UK 2017-12-14 /pmc/articles/PMC5730587/ /pubmed/29242563 http://dx.doi.org/10.1038/s41598-017-17809-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Borgo, Christian
Milan, Gabriella
Favaretto, Francesca
Stasi, Fabio
Fabris, Roberto
Salizzato, Valentina
Cesaro, Luca
Belligoli, Anna
Sanna, Marta
Foletto, Mirto
Prevedello, Luca
Vindigni, Vincenzo
Bardini, Romeo
Donella-Deana, Arianna
Vettor, Roberto
CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity
title CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity
title_full CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity
title_fullStr CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity
title_full_unstemmed CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity
title_short CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity
title_sort ck2 modulates adipocyte insulin-signaling and is up-regulated in human obesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730587/
https://www.ncbi.nlm.nih.gov/pubmed/29242563
http://dx.doi.org/10.1038/s41598-017-17809-w
work_keys_str_mv AT borgochristian ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT milangabriella ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT favarettofrancesca ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT stasifabio ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT fabrisroberto ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT salizzatovalentina ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT cesaroluca ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT belligolianna ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT sannamarta ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT folettomirto ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT prevedelloluca ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT vindignivincenzo ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT bardiniromeo ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT donelladeanaarianna ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity
AT vettorroberto ck2modulatesadipocyteinsulinsignalingandisupregulatedinhumanobesity