[Frontiers in Bioscience E3, 1534-1540, June 1, 2011]

Genistein stimulates the insulin-dependent signaling pathway

Ayumi Haneishi1,2, Katsuhiro Takagi1, Kosuke Asano1,2, Soichiro Nakamura2, Norio Kagawa3, Kazuya Yamada1

1Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan, 2Department of Bioscience and Biotechnology, Shinshu University, 8304 Minamiminowamura, Ina, Nagano 399-4598, Japan, 3Global COE Program, Nagoya University School of Medicine, Nagoya, Aichi 466-8550, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Materials
3.2. Cell culture
3.3. Preparation of total RNA and real-time polymerase chain reactions (PCR)
3.4. Western blot analysis
3.5. Statistical analysis
4. Results
4.1. Induced expression of SHARP-2 mRNA by genistein
4.2. Effects of various pathway inhibitors on genistein-induced SHARP-2 mRNA levels
4.3. Activation of PKCa by genistein
4.4. Genistein acts at the transcriptional level of the rat SHARP-2 gene
5. Discussion
6. Acknowledgements
7. References

1. 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.