NF-kappaB, 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 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-kappaB). 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-kappaB 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-kappaB, GLUT4-Ebox and GLUT4-AT-rich element probes, parallel to the mRNA changes of their respective transcriptional factors NF-kappaB, HIF1-a and MEF2s. Concluding, insulin- and contraction-induced regulation of GLUT4 expression involves distinct transcriptional factors.
Silva
Jose L T
JL
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil.
Giannocco
Gisele
G
Furuya
Daniela T
DT
Lima
Guilherme A
GA
Moraes
Paulo A C
PA
Nachef
Sara
S
Bordin
Silvana
S
Britto
Luiz R G
LR
Nunes
Maria T
MT
Machado
Ubiratan F
UF
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005215:Fasting; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D064326:MEF2 Transcription Factors; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007328:Insulin; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D016328:NF-kappa B; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors