SREBP transcription, insulin induction

Accumulating evidence indicates that SREBP-lc mediates the effect of insulin on transcriptional activation of genes involved in fatty acid synthesis (Horton et ah, 2002 Shimomura et al., 1999 Foretz et al., 1999). When mice are fed with a fat free high-carbohydrate diet, the liver SCD mRNA is induced about 50 fold (Ntambi, 1995 Sessler and Ntambi, 1998), however, the induction is blunted when SREBPl-c is disrupted. Because SDC and D6D mRNA expression were diminished in diabetic rats, and restored by insulin administration (Waters and Ntambi, 1994), the insulin effect on the desaturase genes is likely to be mediated by SREBP-lc. Studies with primary culture rat hepatocytes showed that the expression of a dominant negative SREBPl-c blocked the effect of insulin on the transcriptional activation of SCD, whereas expression of a dominant positive SREBPl-c mimicked the insulin effect (Foretz et al.,... 

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