Genistein stimulates the insulin-dependent signaling pathway

Front Biosci (Elite Ed). 2011 Jun 1;3:1534-40. doi: 10.2741/e354.


Small compounds that activate the insulin-dependent signaling pathway have potential therapeutic applications in controlling insulin-independent diabetes mellitus. In this study, we investigated whether soybean isoflavones could induce the expression of SHARP-2, a downstream component of insulin-dependent signaling pathway, associated with the regulation of blood glucose. One such compound called genistein, rapidly and temporarily induced SHARP-2 mRNA levels in a dose-dependent manner in rat H4IIE hepatoma cells. This induction process was rapidly stimulated by a protein kinase C (PKC) activator and blocked by a PKC inhibitor, suggesting that SHARP-2 may be induced via PKC activation. Upon Western blot analysis, genistein showed a stimulation of PKC phosphorylation. Therefore, we concluded that genistein might transcriptionally induce SHARP-2 through the activation of PKC in H4IIE cells. Our results suggest that genistein might be a useful dietary supplement to control insulin-independent diabetes mellitus by inducing the SHARP-2 expression via a bypass of the insulin-dependent signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Line, Tumor
  • DNA Primers
  • Enzyme Activation
  • Genistein / pharmacology*
  • Insulin / metabolism*
  • Polymerase Chain Reaction
  • Protein Kinase C-alpha / metabolism
  • Rats
  • Signal Transduction / drug effects*
  • Transcription, Genetic / drug effects


  • DNA Primers
  • Insulin
  • Genistein
  • Protein Kinase C-alpha