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 pread ipocyte differentiation by binding and activating peroxisome prolifera tor-activated receptor gamma 2. Although thiazolidinediones are common ly 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 3 T3-L1 adipocytes. Thiazolidinediones induce expression of C/EBP alpha mRNA and protein, while insulin stimulates a rapid decline in C/EBP al pha mRNA and protein. When added in combination, thiazolidinediones bl ock the suppression of C/EBP alpha mRNA by insulin; however, thiazolid inediones do not block the insulin-induced decline in GLUT4 mRNA indic ating 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), sinc e both of these processes occur in the presence of thiazolidinediones. (C) 1998 Academic Press.