Signal Transduction During The Process Of 3T3-L1 Preadipocyte Differentiation And Mitotic Clonal Expansion

During 3T3-L1 preadipocyte differentiation induction, insulinstimulated IGF-1 receptor signal is responsible for the induction of bothadipocyte differentiation and mitotic clonal expansion. Both of these twocellular responses were inhibited with the treatment ofphosphatidylinositol 3-kinase inhibitors, LY294002 or Wortmannin,whereas only mitotic clonal expansion was inhibited with the treatmentof MEK inhibitors, U0126 or PD98059. And PI3K inhibitors only block theactivation of Akt but not ERK, while MEK inhibitors block the activationof ERK not Akt. Of three factors (1-methyl-3-isobutylxanthine,dexamethasone and insulin) inducing 3T3-L1 preadipocyte differentiation,only insulin was able to activate the PI3K-Akt signal cascade. In 3T3-L1preadipocytes, Akt1 RNA interference not only suppressed the expressionof Akt1, but also hormone-induced adipocyte differentiation and mitoticclonal expansion. In Akt1 RNA interfered cells, the signal moleculesupstream of Akt1, such as IGF-1 receptor, insulin receptor substrate-1and PI3K , were activated by insulin stimulation normally, whereas insulin 23T3-L1 前脂肪细胞分化和克隆扩增过程中的信号转导 — Akt1 的重要作用 英文摘要stimulated phosphorylation of forkhead transcription factor(FKHR), whichis a downstream molecule of Akt1, was blocked. Otherwise, the activationof ERK is not attenuated in the Akt1 RNAi cells. Thus, Akt1 is an importantsignal mediator in IGF-1 receptor signal cascade for inducing bothadipocyte differentiation and mitotic clonal expansion. And theinitiation of mitotic clonal expansion need at least two pathways,PI3K-Akt1 and MEK-ERK pathways, to be activated independently at the sametime.