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Diabetes 51:1722-1728, 2002
© 2002 by the American Diabetes Association, Inc.

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

Isabelle Guillet-Deniau1, Virginie Mieulet1, Soazig Le Lay2, Younes Achouri2, Denis Carré1, Jean Girard1, Fabienne Foufelle2, and Pascal Ferré2

1 UPR 1524 CNRS, Institut Cochin de Génétique Moléculaire, Paris, France
2 Unité INSERM 465, Centre de Recherches Biomédicales des Cordeliers, Université Paris VI, Paris, France

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.


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