Abstract
Thiazolidinediones are a class of antidiabetic drugs that induce preadipocyte differentiation by binding and activating peroxisome proliferator-activated receptor γ2. 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 α (C/EBPα) gene expression in fully differentiated 3T3-L1 adipocytes. Thiazolidinediones induce expression of C/EBPα mRNA and protein, while insulin stimulates a rapid decline in C/EBPα mRNA and protein. When added in combination, thiazolidinediones block the suppression of C/EBPα mRNA by insulin; however, thiazolidinediones do not block the insulin-induced decline in GLUT4 mRNA, indicating that repression of C/EBPα mRNA is not required for insulin to suppress expression of a C/EBPα-responsive gene such as GLUT4. Instead, insulin may regulate GLUT4 mRNA by inactivating C/EBPα through dephosphorylation as well as by inducing the expression of the dominant-negative form of C/EBPβ (liver inhibitory protein), since both of these processes occur in the presence of thiazolidinediones.
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More From: Biochemical and Biophysical Research Communications
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