Insulin Inhibits Liver Expression of the CCAAT/Enhancer-Binding Protein β

The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor that is abundant in the liver. The concentration of C/EBPβ mRNA in the liver of mice and rats fed a high-carbohydrate diet, which causes a rise in blood insulin levels, was lower (80 and 65%, respectively) than that detected in animals fed a standard diet. Similarly, the expression of the human insulin gene in the liver of transgenic mice led to a decrease in the concentration of C/EBPβ mRNA. However, no change was detected in the mRNA levels of C/EBα or cAMP regulatory element-binding protein transcription factors in the livers of these mice. Furthermore, the expression of the C/EBPβ gene increased in the liver of diabetic rats and decreased in the liver of diabetic animals treated with vanadate, an insulin mimetic agent. In addition, a decrease in C/EBPβ protein was observed in liver nuclei from mice after insulin injections, in mice fed a high-carbohydrate diet, and in transgenic mice expressing the insulin gene in the liver. These results suggest that insulin might control gene expression in vivo, at least in part, by a mechanism involving a decrease in the transcription factor C/EBPβ.