Soy genistein prevents streptozotocin‐induced diabetes through regulation of pancreatic beta‐cell function

Abstract

Loss of β‐cell mass and function are central to the development of diabetes. In the present study, we found that soy genistein induced clonal and human pancreatic β‐cell proliferation, with 5 µM genistein inducing a maximal 41% increase. The effect of genistein on cell proliferation was neither dependent on estrogen receptors, nor shared by a host of structurally related compounds. Pharmacological or molecular intervention of PKA or ERK1/2 completely abolished the genistein‐stimulated proliferation of INS1 cells and human islets, suggesting that both molecules are essential for genistein action. Consistently, genistein activated cAMP/PKA and ERK1/2 signaling in β‐cells. Furthermore, we found that genistein induced protein expression of cyclin D1, a major cell‐cycle regulator essential for β‐cell growth. We also show that genistein promoted viability, reduced caspase‐3 activity and induced anti‐apoptotic protein Bcl‐2 expression in islet cells. Dietary genistein intake increased plasma levels of insulin and ameliorated hyperglycemia in Streptozotocin (STZ) induced diabetic mice. These effects were associated with improved islet mass and protected islets from STZ‐induced apoptosis in these mice. These findings demonstrate that genistein may be a novel regulator of pancreatic β‐cell function via activation of multiple intracellular signaling pathways, thereby providing an anti‐diabetic effect.