Insulin inhibits liver expression of the CCAAT/enhancer-binding protein beta.
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.
Bosch
F
F
Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Spain.
Sabater
J
J
Valera
A
A
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000096:biosynthesis* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012016:Reference Values; D014157:Transcription Factors / Q000096:biosynthesis*; D014638:Vanadates / Q000494:pharmacology
D001786:Blood Glucose; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014638:Vanadates; D010729:Phosphoenolpyruvate Carboxykinase (GTP)