Usui I, Haruta T, Iwata M, Takano A, Uno T, Kawahara J, Ueno E, Sasaoka T, Kobayashi M
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0194, Japan.
Biochem Biophys Res Commun. 2000 Aug 18;275(1):115-20. doi: 10.1006/bbrc.2000.3201.
In the early phase of adipocyte differentiation, transient increase of DNA synthesis, called clonal expansion, and transient hyperphosphorylation of retinoblastoma protein (Rb) are observed. We investigated the role of these phenomena in insulin-induced adipocyte differentiation of 3T3-L1 cells. Insulin-induced clonal expansion, Rb phosphorylation and adipocyte differentiation were all inhibited by the PI 3-kinase inhibitors and rapamycin, but not the MEK inhibitor, whereas the MEK inhibitor, but not PI 3-kinase inhibitors or rapamycin, decreased c-fos induction. We conclude that insulin induces hyperphosphorylation of Rb via PI 3-kinase and mTOR dependent pathway, which promotes clonal expansion and adipocyte differentiation of 3T3-L1 cells.
在脂肪细胞分化的早期阶段，可观察到DNA合成的短暂增加，即克隆扩增，以及视网膜母细胞瘤蛋白（Rb）的短暂过度磷酸化。我们研究了这些现象在胰岛素诱导的3T3-L1细胞脂肪细胞分化中的作用。PI 3激酶抑制剂和雷帕霉素可抑制胰岛素诱导的克隆扩增、Rb磷酸化和脂肪细胞分化，但MEK抑制剂无此作用；而MEK抑制剂可降低c-fos诱导，PI 3激酶抑制剂和雷帕霉素则无此作用。我们得出结论，胰岛素通过PI 3激酶和mTOR依赖的途径诱导Rb的过度磷酸化，从而促进3T3-L1细胞的克隆扩增和脂肪细胞分化。
