Smad5 regulates Akt2 expression and insulin-induced glucose uptake in L6 myotubes
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2010
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Resumo |
Insulin-induced glucose uptake by skeletal muscle results from Akt2 activation and is severely impaired during insulin resistance Recently, we and others have demonstrated that BMP9 improves glucose homeostasis in diabetic and non-diabetic rodents. However, the mechanism by which BMP9 modulates insulin action remains unknown. Here we demonstrate that Smad5. a transcription factor activated by BMP9, and Akt2. are upregulated in differentiated L6 myotubes. Smad5, rather than Smad1/8, is downregulated ""in vivo"" and ""in vitro"" by dexamethasone Smad5 knockdown decreased Akt2 expression and serine phosphorylation and insulin-induced glucose uptake, and increased the expression of the lipid phosphatase Ship2. Additionally, binding of Smad5 to Akt2 gene is decreased in dexamethasone-treated rats and Increased in L6 myotubes compared to myoblasts The present study indicates that Smad5 regulates glucose uptake in skeletal muscle by controlling Akt2 expression and phosphorylation These finding reveals Smad5 as a potential target for the therapeutic of type 2 diabetes. (C) 2010 Elsevier Ireland Ltd. All rights reserved. FAPESP Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) CNPq Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) National Institute of Obesity and Diabetes (INCT) National Institute of Obesity and Diabetes (INCT) |
Identificador |
MOLECULAR AND CELLULAR ENDOCRINOLOGY, v.319, n.1/Fev, p.30-38, 2010 0303-7207 http://producao.usp.br/handle/BDPI/28032 10.1016/j.mce.2010.01.003 |
Idioma(s) |
eng |
Publicador |
ELSEVIER IRELAND LTD |
Relação |
Molecular and Cellular Endocrinology |
Direitos |
restrictedAccess Copyright ELSEVIER IRELAND LTD |
Palavras-Chave | #Smad5 #Akt2 #Insulin action #Glucose uptake #HUMAN SKELETAL-MUSCLE #BONE MORPHOGENETIC PROTEIN-9 #MICE LACKING #RESISTANCE #DIFFERENTIATION #CELLS #ISOFORM #GROWTH #GLUT4 #IDENTIFICATION #Cell Biology #Endocrinology & Metabolism |
Tipo |
article original article publishedVersion |