Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function

Type 2 diabetes is a result of chronic insulin resistance and loss of functional pancreatic beta-cell mass. Strategies to preserve beta-cell mass and a greater understanding of the mechanisms underlying beta-cell turnover are needed to prevent and treat this devastating disease. Genistein, a naturally occurring soy isoflavone, is reported to have numerous health benefits attributed to multiple biological functions. Over the past 10 years, numerous studies have demonstrated that genistein has anti-diabetic effects, in particular, direct effects on beta-cell proliferation, glucose-stimulated insulin secretion and protection against apoptosis, independent of its functions as an estrogen receptor agonist, antioxidant, or tyrosine kinase inhibitor. Effects are structure-specific and not common to all flavonoids. While there are limited data on the effects of genistein consumption in humans with diabetes, there are a plethora of animal and cell-culture studies that demonstrate a direct effect of genistein on beta-cells at physiologically relevant concentrations (<10 mu M). The effects appear to involve cAMP/PKA signaling and there are some studies that suggest an effect on epigenetic regulation of gene expression. This review focuses on the antidiabetic effects of genistein in both in vitro and in vivo models and potential mechanisms underlying its direct effects on beta-cells.