Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Insulin acutely triggers transcription of Slc2a4 gene: Participation of the AT-rich, E-box and NFKB-binding sites

Texto completo
Autor(es):
Moraes, Paulo Alexandre [1] ; Yonamine, Caio Yogi [1] ; Pinto Junior, Danilo Correa [1] ; DelConti Esteves, Joao Victor [1] ; Machado, Ubiratan Fabres [1] ; Mori, Rosana Cristina [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Life Sciences; v. 114, n. 1, p. 36-44, SEP 26 2014.
Citações Web of Science: 10
Resumo

Aims: The insulin-sensitive glucose transporter protein GLUT4 (solute carrier family 2 member 4 (Slc2a4) gene) plays a key role in glycemic homeostasis. Decreased GLUT4 expression is a current feature in insulin resistant conditions such as diabetes, and the restoration of GLUT4 content improves glycemic control. This study investigated the effect of insulin upon Slc2a4/GLUT4 expression, focusing on the AT-rich element, E-box and nuclear factor NF-kappa-B (NFKB) site. Main methods: Rat soleus muscles were incubated during 180 min with insulin, added or not with wortmannin (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PI3K)-inhibitor), ML9 (serine/threonine protein kinase (AKT) inhibitor) and tumor necrosis factor (TNF, GLUT4 repressor), and processed for analysis of GLUT4 protein (Western blotting); Slc2a4, myocyte enhancer factor 2a/d (Mef2a/d), hypoxia inducible factor 1a (Hif1a), myogenic differentiation 1 (Myod1) and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (Nfkb1) messenger ribonucleic acids (mRNAs) (polymerase chain reaction (PCR)); and AT-rich- (myocyte-specific enhancer factor 2 (MEF2)-binding site), E-box- (hypoxia inducible factor 1 alpha (HIF1A)- and myoblast determination protein 1 (MYOD1)-binding site), and NFKB-binding activity (electrophoretic mobility assay). Key findings: Insulin increased Slc2a4 mRNA expression (140%) and nuclear proteins binding to AT-rich and E-box elements (similar to 90%), all effects were prevented by wortmannin and ML9. Insulin also increased Mef2a/d and Myod1 mRNA expression, suggesting the participation of these transcriptional factors in the Slc2a4 enhancing effect. Conversely, insulin decreased Nflkb1 mRNA expression and protein binding to the NFKB-site (similar to 50%). Furthermore, TNF-induced inhibition of GLUT4 expression (similar to 40%) was prevented by insulin in an NFKB-binding repressing mechanism. GLUT4 protein paralleled the Slc2a4 mRNA regulations. Significance: Insulin enhances the Slc2a4/GLUT4 expression in the skeletal muscle by activating AT-rich and E-box elements, in a PI3K/AKT-dependent mechanism, and repressing NFKB-site activity as well. These results unravel how post-prandial increase of insulin may guarantee GLUT4 expression, and how the insulin signaling impairment can participate in insulin resistance-induced repression of GLUT4. (C) 2014 Elsevier Inc. All rights reserved. (AU)

Processo FAPESP: 07/57873-5 - Participacao da proteina cinase mtor (mammalian target of rapamycin) e do fator transcricional nf-kb na regulacao da expressao do glut4 em musculo soleo de ratos.
Beneficiário:Paulo Alexandre de Carvalho Moraes
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 12/04831-1 - Novos moduladores do controle glicêmico e do desenvolvimento de complicações crônicas no Diabetes mellitus: perspectivas preventivas e terapêuticas
Beneficiário:Ubiratan Fabres Machado
Linha de fomento: Auxílio à Pesquisa - Temático