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

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DOIResolve DOI: http://doi.org/10.1210/en.2009-1294
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleEndocrinology
ISSN0013-7227
1945-7170
Volume151
Issue7
Pages30263037
Subjectdiabetes mellitus; genistein; insulin; mice; pancreas; signal pathway; signal transduction pathways
AbstractGenistein, 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
PublisherOxford University Press
LanguageEnglish
AffiliationNRC Institute for Nutrisciences and Health; National Research Council Canada
Peer reviewedYes
NPARC number23001743
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Record identifier19f27374-de63-42be-83a1-a92b19b32603
Record created2017-03-27
Record modified2017-03-27
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