Hemati N, Erickson R L, Ross S E, Liu R, MacDougald O A
Department of Physiology, University of Michigan Medical Center, Ann Arbor 48109-0622, USA.
Biochem Biophys Res Commun. 1998 Mar 6;244(1):20-5. doi: 10.1006/bbrc.1998.8204.
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.
噻唑烷二酮类是一类抗糖尿病药物，通过结合并激活过氧化物酶体增殖物激活受体γ2来诱导前脂肪细胞分化。尽管噻唑烷二酮类通常被认为是胰岛素增敏剂，但这些药物在完全分化的3T3-L1脂肪细胞中对CCAAT/增强子结合蛋白α（C/EBPα）基因表达具有与胰岛素相反和拮抗的作用。噻唑烷二酮类诱导C/EBPα mRNA和蛋白的表达，而胰岛素则刺激C/EBPα mRNA和蛋白迅速下降。当联合添加时，噻唑烷二酮类可阻断胰岛素对C/EBPα mRNA的抑制作用；然而，噻唑烷二酮类并不阻断胰岛素诱导的葡萄糖转运蛋白4（GLUT4）mRNA下降，这表明胰岛素抑制C/EBPα反应性基因（如GLUT4）的表达并不需要抑制C/EBPα mRNA。相反，胰岛素可能通过去磷酸化使C/EBPα失活以及诱导C/EBPβ（肝脏抑制蛋白）显性负性形式的表达来调节GLUT4 mRNA，因为这两个过程都在噻唑烷二酮类存在的情况下发生。
