SREBPs suppress IRS-2-mediated insulin signalling in the liver

  title={SREBPs suppress IRS-2-mediated insulin signalling in the liver},
  author={Tomohiro Ide and Hitoshi Shimano and Naoya Yahagi and Takashi Matsuzaka and Masanori Nakakuki and Takashi Yamamoto and Yoshimi Nakagawa and Akimitsu Takahashi and Hiroaki Suzuki and Hirohito Sone and Hideo Toyoshima and Akiyoshi Fukamizu and Nobuhiro Yamada},
  journal={Nature Cell Biology},
Insulin receptor substrate 2 (IRS-2) is the main mediator of insulin signalling in the liver, controlling insulin sensitivity. Sterol regulatory element binding proteins (SREBPs) have been established as transcriptional regulators of lipid synthesis. Here, we show that SREBPs directly repress transcription of IRS-2 and inhibit hepatic insulin signalling. The IRS-2 promoter is activated by forkhead proteins through an insulin response element (IRE). Nuclear SREBPs effectively replace and… CONTINUE READING