NF-κB, MEF2A, MEF2D and HIF1-a involvement on insulin- and contraction-induced regulation of GLUT4 gene expression in soleus muscle

The GLUT4 gene transcriptional activity has a profound impact on the insulin-mediated glucose disposal and it is, therefore, important to understand the mechanisms underlying it. Insulin and exercise modulate GLUT4 expression in vivo, but the net control and involved mechanisms of each one have not...

Full description

Saved in:

Bibliographic Details
Published in:	Molecular and cellular endocrinology Vol. 240; no. 1; pp. 82 - 93
Main Authors:	Silva, Jose L.T., Giannocco, Gisele, Furuya, Daniela T., Lima, Guilherme A., Moraes, Paulo A.C., Nachef, Sara, Bordin, Silvana, Britto, Luiz R.G., Nunes, Maria T., Machado, Ubiratan F.
Format:	Journal Article
Language:	English
Published:	Elsevier Ireland Ltd 30-08-2005
Subjects:	EMSA GLUT4 HIF1-a Insulin MEF2 Muscle contraction NF-κB MEF2 NF-κB HIF1-a EMSA GLUT4 Insulin Muscle contraction
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The GLUT4 gene transcriptional activity has a profound impact on the insulin-mediated glucose disposal and it is, therefore, important to understand the mechanisms underlying it. Insulin and exercise modulate GLUT4 expression in vivo, but the net control and involved mechanisms of each one have not been established yet. This paper sought to discriminate, in soleus muscle, the effects of insulin and muscle contraction on GLUT4 gene expression, and the involvement of transcriptional factors: myocite enhancer factor 2 (MEF2 A/C/D), hypoxia inducible factor 1-a (HIF1-a) and nuclear factor-kappa B (NF-κB). The GLUT4 mRNA was reduced by fasting (40%), and increased by in vitro incubation with insulin (25%) or insulin plus glucose (40%), which was accompanied by opposite regulations of NF-κB mRNA. Differently, in vitro, muscle contraction led to a rapid increase (35–80%) in GLUT4, MEF2A, MEF2D and HIF1-a mRNAs. Additionally, electrophoretic mobility shift assay confirmed changes in the binding activity of nuclear proteins to consensus NF-κB, GLUT4-Ebox and GLUT4-AT-rich element probes, parallel to the mRNA changes of their respective transcriptional factors NF-κB, HIF1-a and MEF2s. Concluding, insulin- and contraction-induced regulation of GLUT4 expression involves distinct transcriptional factors.
ISSN:	0303-7207 1872-8057
DOI:	10.1016/j.mce.2005.05.006