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 (SREB P-1c) plays a major role in the effect of insulin on the transcription of h epatic genes such as glucokinase and fatty acid synthase. We show here in c ultured rat hepatocytes that insulin, through activation of the phosphatidy linositol 3-kinase pathway increases the abundance of the precursor form of SREBP-1c in endoplasmic reticulum. This precursor form is then rapidly cle aved, possibly irrespective of the continuous presence of insulin, leading to an increased content of the nuclear mature form of SREBP-1c. Nevertheles s, the increased amount of the mature form of SREBP-1c in the nucleus is no t a prerequisite for the rapid effect of insulin on the transcription of ge nes such as glucokinase, suggesting that additional actions of the hormone are involved, such as the activation of the nuclear form of SRESP-1c or of an unidentified SREBP-1c partner.