Insulin regulation of glucokinase gene expression: evidence against a role for sterol regulatory element binding protein 1 in primary hepatocytes.
Liver key genes for carbohydrate and lipid homeostasis are regulated by insulin and glucose. The sterol regulatory-element binding protein-1c (SREBP-1c) has emerged as a mediator of insulin effects on gene transcription, particularly on glucokinase (GK). In this paper, we show that despite stimulation of GK promoter transcription by overexpression of mature SREBP-1c, insulin induced GK transcription at least 4h ahead of accumulation of mature SREBP-1c in the nucleus. Importantly, the knockdown of SREBP-1 mRNA using a RNA-interference technique reduced the level of nuclear SREBP-1 protein, diminished fatty acid synthase mRNA level, but did not affect GK and L-pyruvate kinase mRNA levels. We concluded that SREBP-1 is unlikely to be the mediator of the early insulin effect on GK gene transcription.
Gregori
Claudine
C
Département d'Endocrinologie, Institut Cochin, Institut National de la santé et de la Recherche Médicale (INSERM) U567, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche 8104, Université René Descartes, 75014 Paris, France.
Guillet-Deniau
Isabelle
I
Girard
Jean
J
Decaux
Jean-François
JF
Pichard
Anne-Lise
AL
D000818:Animals; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D007328:Insulin; D034741:RNA, Small Interfering; D051780:Sterol Regulatory Element Binding Protein 1; D005941:Glucokinase