Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1038/s41598-018-26482-6 http://hdl.handle.net/11449/164809 |
Resumo: | Little is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2 alpha 4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2 alpha 4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2.5 to 7.5 hours. In vivo, AGE-albumin induced whole-body insulin resistance; decreased (similar to 30%) Slc2 alpha 4 mRNA and GLUT4 protein content; and increased (similar to 30%) the nuclear content of nuclear factor NF-kappa-B p50 subunit (NFKB1), and cellular content of 78 kDa glucose-regulated protein (GRP78). In vitro, incubation with AGE-albumin decreased (similar to 50%) the Slc2 alpha 4/GLUT4 content; and increased cellular content of GRP78/94, phosphorylated-IKK-alpha/beta, nuclear content of NFKB1 and RELA, and the nuclear protein binding into Slc2 alpha 4 promoter NFKB-binding site. The data reveal that AGEs impair glucose homeostasis in non-diabetic states of increased AGEs concentration; an effect that involves activation of endoplasmic reticulum-and inflammatory-stress and repression of Slc2 alpha 4/GLUT4 expression. |
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Repositório Institucional da UNESP |
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Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expressionLittle is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2 alpha 4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2 alpha 4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2.5 to 7.5 hours. In vivo, AGE-albumin induced whole-body insulin resistance; decreased (similar to 30%) Slc2 alpha 4 mRNA and GLUT4 protein content; and increased (similar to 30%) the nuclear content of nuclear factor NF-kappa-B p50 subunit (NFKB1), and cellular content of 78 kDa glucose-regulated protein (GRP78). In vitro, incubation with AGE-albumin decreased (similar to 50%) the Slc2 alpha 4/GLUT4 content; and increased cellular content of GRP78/94, phosphorylated-IKK-alpha/beta, nuclear content of NFKB1 and RELA, and the nuclear protein binding into Slc2 alpha 4 promoter NFKB-binding site. The data reveal that AGEs impair glucose homeostasis in non-diabetic states of increased AGEs concentration; an effect that involves activation of endoplasmic reticulum-and inflammatory-stress and repression of Slc2 alpha 4/GLUT4 expression.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Carboidrato & Radioimunoensaio LIM 18, Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Lipides LIM 10, Sao Paulo, SP, BrazilUniv Estadual Paulista, Fac Sci & Technol, Dept Physiotherapy, Sao Paulo, BrazilUniv Nove Julho UNINOVE, Programa Posgrad Med, Sao Paulo, BrazilUniv Estadual Paulista, Fac Sci & Technol, Dept Physiotherapy, Sao Paulo, BrazilFAPESP: 2012/20432-0FAPESP: 2016/25155-5FAPESP: 2012/18724-2FAPESP: 2013/00713-7FAPESP: 2014/17251-9CNPq: 2016/15603-0Nature Publishing GroupUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Univ Nove Julho UNINOVEPinto-Junior, Danilo C.Silva, Karolline S.Michalani, Maria L.Yonamine, Caio Y.Esteves, Joao V.Fabre, Nelly T.Thieme, KarinaCatanozi, SergioOkamoto, Maristela M.Seraphim, Patricia M. [UNESP]Correa-Giannella, Maria L.Passarelli, MarisaMachado, Ubiratan F.2018-11-26T22:38:13Z2018-11-26T22:38:13Z2018-05-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://dx.doi.org/10.1038/s41598-018-26482-6Scientific Reports. London: Nature Publishing Group, v. 8, 11 p., 2018.2045-2322http://hdl.handle.net/11449/16480910.1038/s41598-018-26482-6WOS:000433059900019WOS000433059900019.pdf04110085990708710000-0003-2145-6640Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScientific Reports1,533info:eu-repo/semantics/openAccess2023-12-10T06:21:03Zoai:repositorio.unesp.br:11449/164809Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-10T06:21:03Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression |
title |
Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression |
spellingShingle |
Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression Pinto-Junior, Danilo C. |
title_short |
Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression |
title_full |
Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression |
title_fullStr |
Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression |
title_full_unstemmed |
Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression |
title_sort |
Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression |
author |
Pinto-Junior, Danilo C. |
author_facet |
Pinto-Junior, Danilo C. Silva, Karolline S. Michalani, Maria L. Yonamine, Caio Y. Esteves, Joao V. Fabre, Nelly T. Thieme, Karina Catanozi, Sergio Okamoto, Maristela M. Seraphim, Patricia M. [UNESP] Correa-Giannella, Maria L. Passarelli, Marisa Machado, Ubiratan F. |
author_role |
author |
author2 |
Silva, Karolline S. Michalani, Maria L. Yonamine, Caio Y. Esteves, Joao V. Fabre, Nelly T. Thieme, Karina Catanozi, Sergio Okamoto, Maristela M. Seraphim, Patricia M. [UNESP] Correa-Giannella, Maria L. Passarelli, Marisa Machado, Ubiratan F. |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) Univ Nove Julho UNINOVE |
dc.contributor.author.fl_str_mv |
Pinto-Junior, Danilo C. Silva, Karolline S. Michalani, Maria L. Yonamine, Caio Y. Esteves, Joao V. Fabre, Nelly T. Thieme, Karina Catanozi, Sergio Okamoto, Maristela M. Seraphim, Patricia M. [UNESP] Correa-Giannella, Maria L. Passarelli, Marisa Machado, Ubiratan F. |
description |
Little is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2 alpha 4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2 alpha 4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2.5 to 7.5 hours. In vivo, AGE-albumin induced whole-body insulin resistance; decreased (similar to 30%) Slc2 alpha 4 mRNA and GLUT4 protein content; and increased (similar to 30%) the nuclear content of nuclear factor NF-kappa-B p50 subunit (NFKB1), and cellular content of 78 kDa glucose-regulated protein (GRP78). In vitro, incubation with AGE-albumin decreased (similar to 50%) the Slc2 alpha 4/GLUT4 content; and increased cellular content of GRP78/94, phosphorylated-IKK-alpha/beta, nuclear content of NFKB1 and RELA, and the nuclear protein binding into Slc2 alpha 4 promoter NFKB-binding site. The data reveal that AGEs impair glucose homeostasis in non-diabetic states of increased AGEs concentration; an effect that involves activation of endoplasmic reticulum-and inflammatory-stress and repression of Slc2 alpha 4/GLUT4 expression. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-11-26T22:38:13Z 2018-11-26T22:38:13Z 2018-05-25 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1038/s41598-018-26482-6 Scientific Reports. London: Nature Publishing Group, v. 8, 11 p., 2018. 2045-2322 http://hdl.handle.net/11449/164809 10.1038/s41598-018-26482-6 WOS:000433059900019 WOS000433059900019.pdf 0411008599070871 0000-0003-2145-6640 |
url |
http://dx.doi.org/10.1038/s41598-018-26482-6 http://hdl.handle.net/11449/164809 |
identifier_str_mv |
Scientific Reports. London: Nature Publishing Group, v. 8, 11 p., 2018. 2045-2322 10.1038/s41598-018-26482-6 WOS:000433059900019 WOS000433059900019.pdf 0411008599070871 0000-0003-2145-6640 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Scientific Reports 1,533 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
11 application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
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Repositório Institucional da UNESP |
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Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1799965238961897472 |