The insulin receptor translocates to the nucleus to regulate cell proliferation in liver

dc.creatorGutiérrez, Maria Jimena Amaya
dc.creatorOliveira, André Gustavo
dc.creatorGuimarães, Erika Sousa
dc.creatorCasteluber, Marisa Cristina Fonseca
dc.creatorCarvalho, Sandhra Maria de
dc.creatorAndrade, Lídia Maria de
dc.creatorPinto, Mauro Cunha Xavier
dc.creatorMennone, Albert
dc.creatorOliveira, Cleida Aparecida de
dc.creatorResende, Rodrigo Ribeiro
dc.creatorMenezes, Gustavo Batista de
dc.creatorNathanson, Michael Harris
dc.creatorLeite, Maria de Fátima
dc.date2015-01-28T11:49:10Z
dc.date2015-01-28T11:49:10Z
dc.date2014
dc.date.accessioned2023-09-27T00:00:12Z
dc.date.available2023-09-27T00:00:12Z
dc.identifierGUTIÉRREZ, 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.
dc.identifier0270-9139
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/9395
dc.identifier10.1002/hep.26609
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8896429
dc.descriptionInsulin’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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherWilliams & Wilkin
dc.rightsopen access
dc.subjectReceptor Tyrosine Kinase
dc.subjectCalcium signaling
dc.subjectInositol 1,4,5,-trisphosphate
dc.subjectLiver regeneration
dc.titleThe insulin receptor translocates to the nucleus to regulate cell proliferation in liver
dc.typeArticle


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