Author | Gutiérrez, Maria Jimena Amaya | |
Author | Oliveira, André Gustavo | |
Author | Guimarães, Erika Sousa | |
Author | Casteluber, Marisa Cristina Fonseca | |
Author | Carvalho, Sandhra Maria de | |
Author | Andrade, Lídia Maria de | |
Author | Pinto, Mauro Cunha Xavier | |
Author | Mennone, Albert | |
Author | Oliveira, Cleida Aparecida de | |
Author | Resende, Rodrigo Ribeiro | |
Author | Menezes, Gustavo Batista de | |
Author | Nathanson, Michael Harris | |
Author | Leite, Maria de Fátima | |
Access date | 2015-01-28T11:49:10Z | |
Available date | 2015-01-28T11:49:10Z | |
Document date | 2014 | |
Citation | GUTIÉRREZ, Maria Jimena Amaya et al. The Insulin Receptor Translocates to the Nucleus to Regulate Cell Proliferation in Liver. Hepatology, v. 59, n. 1, p. 274-283, 2014. | pt_BR |
ISSN | 0270-9139 | |
URI | https://www.arca.fiocruz.br/handle/icict/9395 | |
Language | eng | pt_BR |
Publisher | Williams & Wilkin | pt_BR |
Rights | open access | pt_BR |
Title | The insulin receptor translocates to the nucleus to regulate cell proliferation in liver | pt_BR |
Type | Article | pt_BR |
DOI | 10.1002/hep.26609 | |
Abstract | Insulin’s metabolic effects in the liver are widely appreciated, but insulin’s ability to act as a hepatic mitogen is less well understood. Because the Insulin Receptor (IR) can traffic to the nucleus, and calcium (Ca2+) signals within the nucleus regulate cell proliferation, we investigated whether insulin’s mitogenic effects result from activation of Ca2+ signaling pathways by IRs within the nucleus. Insulin-induced increases in Ca2+ and cell proliferation depended upon clathrin- and caveolin-dependent translocation of the IR to the nucleus, as well as upon formation of inositol 1,4,5,-trisphosphate (InsP3) in the nucleus, whereas insulin’s metabolic effects did not depend on either of these events. Moreover, liver regeneration after partial hepatectomy also depended upon formation of InsP3 in the nucleus but not the cytosol, whereas hepatic glucose metabolism was not affected by buffering InsP3 in the nucleus. Conclusion: These findings provide evidence that insulin’s mitogenic effects are mediated by a subpopulation of IRs that traffic to the nucleus to locally activate InsP3-dependent Ca2+ signaling pathways. The steps along this signaling pathway reveal a number of potential targets for therapeutic modulation of liver growth in health and disease. | pt_BR |
Affilliation | Yale University. Department of Internal Medicine. Section of Digestive Diseases. New Haven, CT, USA. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Faculdade de Engenharia. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil / Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Yale University. Department of Internal Medicine. Section of Digestive Diseases. New Haven, CT, USA. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Yale University. Department of Internal Medicine. Section of Digestive Diseases. New Haven, CT, USA. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil / Howard Hughes Medical Institute. Chevy Chase, EUA. | pt_BR |
Subject | Receptor Tyrosine Kinase | pt_BR |
Subject | Calcium signaling | pt_BR |
Subject | Inositol 1,4,5,-trisphosphate | pt_BR |
Subject | Liver regeneration | pt_BR |