title: Genistein stimulates the insulin-dependent signaling pathway.
abstract: 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.
authors.affiliation: Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, Matsumoto, Nagano, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Haneishi
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takagi
authors.forename: Kosuke
authors.initials: K
authors.lastname: Asano
authors.forename: Soichiro
authors.initials: S
authors.lastname: Nakamura
authors.forename: Norio
authors.initials: N
authors.lastname: Kagawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D004789:Enzyme Activation; D019833:Genistein / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D017931:DNA Primers; D007328:Insulin; D019833:Genistein; D051571:Protein Kinase C-alpha