Genistein induces pancreatic beta-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice
Language: 
English
Abstract: 

Genistein, a flavonoid in legumes and some herbal medicines, has various biological actions. However, studies on whether genistein has an effect on pancreatic beta-cell function are very limited. In the present study, we investigated the effect of genistein on beta-cell proliferation and cellular signaling related to this effect and further determined its antidiabetic potential in insulin-deficient diabetic mice. Genistein induced both INS1 and human islet beta-cell proliferation after 24 h of incubation, with 5 mum genistein inducing a maximal 27% increase. The effect of genistein on beta-cell proliferation was neither dependent on estrogen receptors nor shared by 17beta-estradiol or a host of structurally related flavonoid compounds. Pharmacological or molecular intervention of protein kinase A (PKA) or ERK1/2 completely abolished genistein-stimulated beta-cell proliferation, suggesting that both molecules are essential for genistein action. Consistent with its effect on cell proliferation, genistein induced cAMP/PKA signaling and subsequent phosphorylation of ERK1/2 in both INS1 cells and human islets. Furthermore, genistein induced protein expression of cyclin D1, a major cell-cycle regulator essential for beta-cell growth. Dietary intake of genistein significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in streptozotocin-induced diabetic mice, concomitant with improved islet beta-cell proliferation, survival, and mass. These results demonstrate that genistein may be a natural antidiabetic agent by directly modulating pancreatic beta-cell function via activation of the cAMP/PKA-dependent ERK1/2 signaling pathway.

Author(s): 
Fu, Zhuo
Zhang, Wen
Zhen, Wei
Lum, Hazel
Nadler, Jerry
Bassaganya-Riera, Josep
Jia, Zhenquan
Wang, Yanwen
Misra, Hara
Liu, Dongmin
Item Type: 
Journal Article
Publication Title: 
Endocrinology
Journal Abbreviation: 
Endocrinology
Publication Date: 
Jul 2010
Publication Year: 
2010
Pages: 
3026-3037
Volume: 
151
Issue: 
7
ISSN: 
1945-7170
DOI: 
10.1210/en.2009-1294
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 20484465 PMCID: PMC2903942

Turabian/Chicago Citation

Zhuo Fu, Wen Zhang, Wei Zhen, Hazel Lum, Jerry Nadler, Josep Bassaganya-Riera, Zhenquan Jia, Yanwen Wang, Hara Misra and Dongmin Liu. Jul 2010. "Genistein induces pancreatic beta-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice." Endocrinology 151: 7: 3026-3037. 10.1210/en.2009-1294.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1210/en.2009-1294 | issn = 1945-7170 | volume = 151 | pages = 3026-3037 | last = Fu | first = Zhuo | coauthors = Zhang, Wen, Zhen, Wei, Lum, Hazel, Nadler, Jerry, Bassaganya-Riera, Josep, Jia, Zhenquan, Wang, Yanwen, Misra, Hara, Liu, Dongmin | title = Genistein induces pancreatic beta-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice | journal = Endocrinology | date = Jul 2010 | pmid = | pmc = }} </ref>