Genistein induces pancreatic β-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice

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DOI	Resolve DOI: https://doi.org/10.1210/en.2009-1294
Author	Search for: Fu, Zhuo; Search for: Zhang, Wen; Search for: Zhen, Wei; Search for: Lum, Hazel; Search for: Nadler, Jerry; Search for: Bassaganya-riera, Josep; Search for: Jia, Zhenquan; Search for: Wang, Yanwen¹; Search for: Misra, Hara; Search for: Liu, Dongmin
Name affiliation	National Research Council of Canada. NRC Institute for Nutrisciences and Health
Format	Text, Article
Journal title	Endocrinology
ISSN	0013-7227 1945-7170
Volume	151
Issue	7
Pages	3026–3037
Subject	diabetes mellitus; genistein; insulin; mice; pancreas; signal pathway; signal transduction pathways
Abstract	Genistein, a flavonoid in legumes and some herbal medicines, has various biological actions. However, studies on whether genistein has an effect on pancreatic β-cell function are very limited. In the present study, we investigated the effect of genistein on β-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 β-cell proliferation after 24 h of incubation, with 5 μm genistein inducing a maximal 27% increase. The effect of genistein on β-cell proliferation was neither dependent on estrogen receptors nor shared by 17β-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 β-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 β-cell growth. Dietary intake of genistein significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in streptozotocin-induced diabetic mice, concomitant with improved islet β-cell proliferation, survival, and mass. These results demonstrate that genistein may be a natural antidiabetic agent by directly modulating pancreatic β-cell function via activation of the cAMP/PKA-dependent ERK1/2 signaling pathway.
Publication date	2010-07
Publisher	Oxford University Press
Language	English
Peer reviewed	Yes
NPARC number	23001743
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Record identifier	19f27374-de63-42be-83a1-a92b19b32603
Record created	2017-03-27
Record modified	2020-05-30

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