HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, D. Articles by Reynolds, K. A. Search for Related Content PubMed PubMed Citation Articles by Liu, D. Articles by Reynolds, K. A. Social Bookmarking                What's this?

Genistein Acutely Stimulates Insulin Secretion in Pancreatic ß-Cells Through a cAMP-Dependent Protein Kinase Pathway

¹ Department of Human Nutrition, Foods, and Exercise, College of Agriculture and Life Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia
² Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Charlottesville, Virginia

Address correspondence and reprint requests to Dongmin Liu, Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060. E-mail: doliu{at}vt.edu

Abbreviations: GLP-1, glucagon-like peptide-1; GSIS, glucose-stimulated insulin secretion; IBMX, isobutylmethylxanthine; KRBB, Krebs-Ringer bicarbonate buffer; PDE, phosphodiesterase; PKA, protein kinase A; PKAC and PKACß, PKA catalytic subunits and ß; PTK, protein tyrosine kinase; RIA, radioimmunoassay; siRNA, small interfering RNA

Although genistein, a soy isoflavone, has beneficial effects on various tissues, it is unclear whether it plays a role in physiological insulin secretion. Here, we present evidence that genistein increases rapid glucose-stimulated insulin secretion (GSIS) in both insulin-secreting cell lines (INS-1 and MIN6) and mouse pancreatic islets. Genistein elicited a significant effect at a concentration as low as 10 nmol/l with a maximal effect at 5 µmol/l. The effect of genistein on GSIS was not dependent on estrogen receptor and also not related to an inhibition of protein tyrosine kinase (PTK). Consistent with its effect on GSIS, genistein increases intracellular cAMP and activates protein kinase A (PKA) in both cell lines and the islets by a mechanism that does not involve estrogen receptor or PTK. The induced cAMP by genistein, at physiological concentrations, may result primarily from enhanced adenylate cyclase activity. Pharmacological or molecular intervention of PKA activation indicated that the insulinotropic effect of genistein is primarily mediated through PKA. These findings demonstrated that genistein directly acts on pancreatic ß-cells, leading to activation of the cAMP/PKA signaling cascade to exert an insulinotropic effect, thereby providing a novel role of soy isoflavones in the regulation of insulin secretion.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Noriega-Lopez, A. R. Tovar, M. Gonzalez-Granillo, R. Hernandez-Pando, B. Escalante, P. Santillan-Doherty, and N. Torres Pancreatic Insulin Secretion in Rats Fed a Soy Protein High Fat Diet Depends on the Interaction between the Amino Acid Pattern and Isoflavones J. Biol. Chem., July 13, 2007; 282(28): 20657 - 20666. [Abstract] [Full Text] [PDF]

				F. F. Dai, Y. Zhang, Y. Kang, Q. Wang, H. Y. Gaisano, K.-H. Braunewell, C. B. Chan, and M. B. Wheeler The Neuronal Ca2+ Sensor Protein Visinin-like Protein-1 Is Expressed in Pancreatic Islets and Regulates Insulin Secretion J. Biol. Chem., August 4, 2006; 281(31): 21942 - 21953. [Abstract] [Full Text] [PDF]