Insulin inhibits liver expression of the CCAAT/enhancer-binding protein beta.
ABSTRACT The CCAAT/enhancer-binding protein beta (C/EBP beta) is a transcription factor that is abundant in the liver. The concentration of C/EBP beta 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/EBP beta mRNA. However, no change was detected in the mRNA levels of C/EBP alpha or cAMP regulatory element-binding protein transcription factors in the livers of these mice. Furthermore, the expression of the C/EBP beta 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/EBP beta 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/EBP beta.
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ABSTRACT: Summary There is a significant body of evidence which suggests that the α-isoform of the CCAAT/enhancer binding protein (C/EBPα) plays a central regulatory role in energy metabolism in the liver. However, there is little information available regarding regulation of its expression in this tissue. In this study, we examined the effect of hormones and diabetes on its expression in rat H4IIE hepatoma cells and in rat liver. Treatment of H4IIE cells with dexamethasone led to a threefold increase in C/EBPα mRNA within 4 h. Insulin treatment produced a bi-phasic response, initially reducing mRNA levels up to the 4 h time point, but after 8 h a twofold increase in C/EBPα mRNA was observed. Treatment with 8-chlorophenylthio-cAMP produced a twofold induction of C/EBPα mRNA after 8 h. Western analysis indicated that the changes in mRNA in response to hormonal treatment generally resulted in corresponding alterations in C/EBPα protein levels. Finally, we observed an inhibition of C/EBPα gene expression in streptozotocin-diabetic rat liver, reflected by a decrease in both mRNA and protein levels that were partially reversed by insulin treatment. These results indicate that the expression of C/EBPα in liver is under complex control by both hormonal and metabolic signals, which is consistent with its role as a trans -regulator of genes which play a role in energy metabolism. [Diabetologia (1997) 40: 1117–1124]Diabetologia 09/1997; 40(10):1117-1124. · 6.88 Impact Factor
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ABSTRACT: Neurodegeneration is one of the most important complications of diabetes mellitus (DM). The exact mechanisms underlying neurodegeneration related to diabetic complications such as cognitive deficits and peripheral neuropathy are not clarified yet. Due to the fact that CCAAT/enhancer binding proteins (C/EBPs) have roles in cognitive functions, memory, synaptic plasticity, inflammation, lipid storage, and response to neurotrophic factors, it is possible to suggest that these transcription factors could have roles in neurodegeneration. Hence, in this study, the effects of experimental diabetes on C/EBPs in the hippocampus, sciatic nerve, and ganglia tissues were examined. After experimentally induced diabetes, immunoreactivity of related proteins was measured by western blotting. C/EBPα immunoreactivity in the hippocampus was not altered at 4-weeks but significantly decreased at 12-weeks of diabetes. C/EBPβ immunoreactivity was not altered at 4-weeks whereas significantly increased at 12-weeks of diabetes. In the ganglion, C/EBPα immunoreactivity was significantly decreased in diabetes, but C/EBPβ immunoreactivity was not affected. In the sciatic nerve, C/EBPα and β immunoreactivities were significantly decreased in diabetic rats. Furthermore, insulin therapy prevented diabetes-induced alterations in C/EBPα and β immunoreactivities. This study indicated, for the first time, that DM altered the immunoreactivity of C/EBPs in the nervous system. C/EBPs might be one of the important molecular targets which are responsible for neurodegeneration seen in diabetes.Cellular and Molecular Neurobiology 03/2013; 33(4). · 2.20 Impact Factor
- Journal of Biological Chemistry 01/2000; 275(19):14173-14181. · 4.60 Impact Factor