The class
Insulin fails to activate the CETP gene promoter in transfected rat fibroblasts, despite a role for C/EBPalpha (Mol Cell Biochem 2000)
Original title: Insulin does not regulate the promoter of cholesteryl ester transfer protein (CETP) in HIRc/pCETP-CAT cells
Testing the hypothesis that insulin regulates CETP gene expression via CCAAT/enhancer binding protein alpha (C/EBPalpha), researchers stably transfected rat fibroblasts expressing the human insulin receptor with a construct linking 3.2 kb of the CETP promoter to a reporter gene (pCETP-CAT). Reporter activity was 8-fold higher when cells were cultured with 100 mg/dL LDL cholesterol than without it (P less than 0.05), and transient expression of C/EBPalpha produced a 3-fold increase in reporter activity compared to nonspecific DNA (P less than 0.05). However, culturing cells with 100 nM insulin produced no change in reporter activity relative to controls, and insulin had no observable effect on the CETP promoter even in cells expressing C/EBPalpha, failing to substantiate the hypothesis that insulin regulates CETP transcription through this pathway.
Original abstract
Cholesteryl ester transfer protein (CETP) is a plasma enzyme involved in cholesterol metabolism. As a potential target in the treatment of atherosclerosis, a number of studies have focused how this enzyme is regulated. It has been postulated that insulin may regulate CETP gene expression, and these effects may be mediated through CCAAT/enhancer binding protein alpha (C/EBPalpha). The present study examines the effects of insulin on the activity of the CETP promoter in rat fibroblasts expressing the human insulin receptor (HIRc). HIRc cells were stably transfected with a chimeric construct containing 3.2 kb of the CETP promoter attached to the bacterial chloramphenicol acyltransferase gene (pCETP-CAT) without significantly affecting the expression of the insulin receptor. CAT activity was 8-fold higher in cultured HIRc/pCETP-CAT in the presence of 100 mg/dL LDL cholesterol, than those cultured without cholesterol (p < 0.05). However, culturing these cells in the presence of 100 nM insulin did not result in any change in CAT activity when compared to control cells. In HIRc/pCETP-CAT cells transiently transfected with a construct that constitutively expressed C/EBPalpha protein, a 3-fold increase in CAT activity was observed when compared to cells transiently transfected with non-specific DNA (p < 0.05). However, no observable effect on the CETP promoter was observed in the presence of insulin. Thus, in HIRc/pCETP-CAT cells, we were unable to substantiate the hypothesis that insulin regulates CETP gene transcription. These results suggest that the effects of insulin on CETP expression regulation may be downstream of transcription.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.