Sterol regulatory element binding protein-1c expression and action in rat muscles: insulin-like effects on the control of glycolytic and lipogenic enzymes and UCP3 gene expression.
Sterol regulatory element binding protein-1c (SREBP-1c) is a transcription factor that mediates insulin effects on hepatic gene expression. It is itself transcriptionally stimulated by insulin in hepatocytes. Here we show that SREBP-1c mRNA is expressed in adult rat skeletal muscles and that this expression is decreased by diabetes. The regulation of SREBP-1c expression was then assessed in cultures of adult muscle satellite cells. These cells form spontaneously contracting multinucleated myotubes within 7 days of culture. SREBP-1c mRNA is expressed in contracting myotubes. A 4-h treatment with 100 nmol/l insulin increases SREBP-1c expression and nuclear abundance by two- to threefold in myotubes. In cultured myotubes, insulin increases the expression of glycolytic and lipogenic enzyme genes and inhibits the 9-cis retinoic acid-induced UCP3 expression. These effects of insulin are mimicked by adenovirus-mediated expression of a transcriptionally active form of SREBP-1c. We conclude that in skeletal muscles, SREBP-1c expression is sensitive to insulin and can transduce the positive and negative actions of the hormone on specific genes and thus has a pivotal role in long-term muscle insulin sensitivity.
Guillet-Deniau
Isabelle
I
UPR 1524 CNRS, Institut Cochin de Génétique Moléculaire, Paris, France. guillet-deniau@cochin.inserm.fr
Mieulet
Virginie
V
Le Lay
Soazig
S
Achouri
Younes
Y
Carré
Denis
D
Girard
Jean
J
Foufelle
Fabienne
F
Ferré
Pascal
P
D000077556:Alitretinoin; D000818:Animals; D015152:Blotting, Northern; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D007473:Ion Channels; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000737:chemistry / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D000071247:Uncoupling Protein 3
D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D007473:Ion Channels; D008055:Lipids; D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D000077556:Alitretinoin; D014212:Tretinoin