Genistein Induces Pancreatic beta-Cell Proliferation through Activation of Multiple Signaling Pathways and Prevents Insulin-Deficient Diabetes in Mice

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dc.contributor.authorFu, Zhuoen
dc.contributor.authorZhang, Wenen
dc.contributor.authorZhen, Weien
dc.contributor.authorLum, Hazelen
dc.contributor.authorNadler, Jerryen
dc.contributor.authorBassaganya-Riera, Josepen
dc.contributor.authorJia, Zhenquanen
dc.contributor.authorWang, Yanwenen
dc.contributor.authorMisra, Hara P.en
dc.contributor.authorLiu, Dongminen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessed2014-07-07en
dc.date.accessioned2014-07-08T13:02:16Zen
dc.date.available2014-07-08T13:02:16Zen
dc.date.issued2010-07en
dc.description.abstractGenistein, 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 mu M genistein inducing a maximal 27% increase. The effect of genistein on beta-cell proliferation was neither dependent on estrogen receptors nor shared by 17 beta-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. (Endocrinology 151: 3026-3037, 2010)en
dc.description.sponsorshipAmerican Diabetes Associationen
dc.description.sponsorshipVirginia Commonwealth Health Research Boarden
dc.description.sponsorshipNational Institutes of Health 1R21AT004694, R01 DK55240en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationZhuo Fu, Wen Zhang, Wei Zhen, Hazel Lum, Jerry Nadler, Josep Bassaganya-Riera, Zhenquan Jia, Yanwen Wang, Hara Misra, and Dongmin Liu. "Genistein Induces Pancreatic β-Cell Proliferation through Activation of Multiple Signaling Pathways and Prevents Insulin-Deficient Diabetes in Mice," Endocrinology 2010 151:7, 3026-3037. DOI: http://dx.doi.org/10.1210/en.2009-1294.en
dc.identifier.doihttps://doi.org/10.1210/en.2009-1294en
dc.identifier.issn0013-7227en
dc.identifier.urihttp://hdl.handle.net/10919/49388en
dc.identifier.urlhttp://press.endocrine.org/doi/abs/10.1210/en.2009-1294en
dc.language.isoenen
dc.publisherEndocrine Societyen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectglucagon-like peptide-1en
dc.subjecttyrosine kinase inhibitorsen
dc.subjectdependenten
dc.subjectprotein-kinaseen
dc.subjectcamp-responsive elementen
dc.subjectoxidative stressen
dc.subjectsoyen
dc.subjectisoflavonesen
dc.subjectpostmenopausal womenen
dc.subjectquantitative-analysisen
dc.subjectsoybeanen
dc.subjectisoflavonesen
dc.subjectcombination therapyen
dc.subjectendocrinology & metabolismen
dc.titleGenistein Induces Pancreatic beta-Cell Proliferation through Activation of Multiple Signaling Pathways and Prevents Insulin-Deficient Diabetes in Miceen
dc.title.serialEndocrinologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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