Sun Cheng, Zhou Jia
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing 210061, China.
Biochem Pharmacol. 2008 Jul 1;76(1):120-7. doi: 10.1016/j.bcp.2008.04.004. Epub 2008 Apr 16.
Previous study showed that Trichostatin A (TSA) could improve insulin receptor substrate 1 (IRS-1) phosphorylation at tyrosine in response to insulin evocation. However, the effects of TSA on insulin stimulated glucose utilization and insulin signaling transduction are still poorly understood. Here we showed that TSA significantly enhanced insulin stimulated glucose uptake, glycogen synthesis and glycogen synthase activities in C2C12 myotubes. In addition, the insulin stimulated phosphorylations in insulin receptor, Akt and GSK3beta were remarkably increased in the TSA-treated cells. These improving effects of TSA were probably due to HDAC2 inhibition, since the enhanced expression of HDAC2 could abolish the TSA-induced improvement in the insulin signaling transduction. Moreover, HDAC2 knockdown as well as TSA treatment also improved insulin stimulated glycogen synthesis. Most importantly, no additional effect of TSA on insulin stimulated glycogen synthesis was observed in the HDAC2 downregulated cells. These data suggest that HDAC2 should be an important potential target for regulating insulin sensitivity.
先前的研究表明，曲古抑菌素A（TSA）可在胰岛素激发时改善胰岛素受体底物1（IRS-1）酪氨酸磷酸化。然而，TSA对胰岛素刺激的葡萄糖利用和胰岛素信号转导的影响仍知之甚少。在此我们表明，TSA显著增强了C2C12肌管中胰岛素刺激的葡萄糖摄取、糖原合成和糖原合酶活性。此外，在TSA处理的细胞中，胰岛素刺激的胰岛素受体、Akt和GSK3β磷酸化显著增加。TSA的这些改善作用可能是由于HDAC2抑制，因为HDAC2表达增强可消除TSA诱导的胰岛素信号转导改善。此外，HDAC2敲低以及TSA处理也改善了胰岛素刺激的糖原合成。最重要的是，在HDAC2下调的细胞中未观察到TSA对胰岛素刺激的糖原合成有额外作用。这些数据表明，HDAC2应是调节胰岛素敏感性的重要潜在靶点。
