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Insulin regulation of glucokinase gene expression: Evidence against a role for sterol regulatory element binding protein 1 in primary hepatocytes
Author(s) -
Gregori Claudine,
Guillet-Deniau Isabelle,
Girard Jean,
Decaux Jean-François,
Pichard Anne-Lise
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.032
Subject(s) - glucokinase , sterol regulatory element binding protein , gene knockdown , biology , transcription factor , transcription (linguistics) , mediator , glucose homeostasis , microbiology and biotechnology , insulin , chemistry , biochemistry , medicine , endocrinology , gene , insulin resistance , linguistics , philosophy
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 4 h 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.