Trichostatin A improves insulin stimulated glucose utilization and insulin signaling transduction through the repression of HDAC2.
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.
Sun
Cheng
C
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing 210061, China. suncheng@nicemice.cn
Zhou
Jia
J
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006006:Glycogen Synthase / Q000378:metabolism; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation; D034741:RNA, Small Interfering; D011972:Receptor, Insulin / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007328:Insulin; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C012589:trichostatin A; D006003:Glycogen; D006006:Glycogen Synthase; D011972:Receptor, Insulin; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2; D005947:Glucose