Regulation of CCAAT/enhancer binding protein alpha (C/EBP alpha) gene expression by thiazolidinediones in 3T3-L1 adipocytes.
Thiazolidinediones are a class of antidiabetic drugs that induce preadipocyte differentiation by binding and activating peroxisome proliferator-activated receptor gamma 2. Although thiazolidinediones are commonly thought of as insulin-sensitizing agents, these drugs have opposing and antagonistic effects to that of insulin on CCAAT/enhancer binding protein alpha (C/EBP alpha) gene expression in fully differentiated 3T3-L1 adipocytes. Thiazolidinediones induce expression of C/EBP alpha mRNA and protein, while insulin stimulates a rapid decline in C/EBP alpha mRNA and protein. When added in combination, thiazolidinediones block the suppression of C/EBP alpha mRNA by insulin; however, thiazolidinediones do not block the insulin-induced decline in GLUT4 mRNA, indicating that repression of C/EBP alpha mRNA is not required for insulin to suppress expression of a C/EBP alpha-responsive gene such as GLUT4. Instead, insulin may regulate GLUT4 mRNA by inactivating C/EBP alpha through dephosphorylation as well as by inducing the expression of the dominant-negative form of C/EBP beta (liver inhibitory protein), since both of these processes occur in the presence of thiazolidinediones.
Hemati
N
N
Department of Physiology, University of Michigan Medical Center, Ann Arbor 48109-0622, USA.
Erickson
R L
RL
Ross
S E
SE
Liu
R
R
MacDougald
O A
OA
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D009124:Muscle Proteins; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D007329:Insulin Antagonists; D008024:Ligands; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D013844:Thiazoles; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione