Regulation of sterol regulatory-element binding protein 1 gene expression in liver: role of insulin and protein kinase B/cAkt

摘要: Insulin stimulates the transcription of sterol regulatory- element binding protein (SREBP) 1/ADD1 gene in liver. Hepatocytes primary culture were used to delineate insulin signalling pathway for induction SREBP1 expression. The inhibitors phosphoinositide 3-kinase (PI 3-kinase), wortmannin and LY 294002, abolished insulin-dependent increase mRNA, whereas inhibitor mitogen- activated kinase cascade, PD 98059, was without effect. To investigate role B (PKB)/cAkt downstream PI 3-kinase, hepatocytes transduced with an adenovirus encoding a PKB--oestrogen receptor fusion protein. PKB activity this recombinant rapidly challenged 4-hydroxytamoxifen (OHT), as endogenous insulin. addition OHT resulted accumulation time-course magnitude similar effect non-transduced cells. level mRNA not increased by expressing mutant form whose OHT. Thus acute activation is sufficient induce hepatocytes, might be major event which induces expression