Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes.
The transcription factor sterol regulatory-element-binding protein-1c (SREBP-1c) plays a major role in the effect of insulin on the transcription of hepatic genes such as glucokinase and fatty acid synthase. We show here in cultured rat hepatocytes that insulin, through activation of the phosphatidylinositol 3-kinase pathway increases the abundance of the precursor form of SREBP-1c in endoplasmic reticulum. This precursor form is then rapidly cleaved, possibly irrespective of the continuous presence of insulin, leading to an increased content of the nuclear mature form of SREBP-1c. Nevertheless, the increased amount of the mature form of SREBP-1c in the nucleus is not a prerequisite for the rapid effect of insulin on the transcription of genes such as glucokinase, suggesting that additional actions of the hormone are involved, such as the activation of the nuclear form of SREBP-1c or of an unidentified SREBP-1c partner.
Azzout-Marniche
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U465 INSERM, Centre de Recherches Biomédicales des Cordeliers (Université Paris 6), 15, rue de l'Ecole de Médecine, 75270, Paris Cedex 06, France.
Bécard
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Guichard
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Foretz
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Ferré
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Foufelle
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D000818:Animals; D015152:Blotting, Northern; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005941:Glucokinase / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1; D013997:Time Factors; D014157:Transcription Factors; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007328:Insulin; D011498:Protein Precursors; D011500:Protein Synthesis Inhibitors; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D003513:Cycloheximide; D019869:Phosphatidylinositol 3-Kinases; D005941:Glucokinase