Genistein ameliorates hyperglycemia in a mouse model of nongenetic type 2 diabetes

While peripheral insulin resistance is common during obesity and aging in mice and people, the progression to type 2 diabetes (T2D) is largely due to loss of beta-cell mass and function through apoptosis. We recently reported that genistein, a soy derived isoflavone, can improve glycemic control and beta-cell function in insulin-deficient diabetic mice. However, whether it can prevent beta-cell loss and diabetes in T2D mice is unknown. Our current study aimed to investigate the effect of dietary supplemented genistein in a nongenetic T2D mouse model. Nongenetic, middle-aged obese diabetic mice were generated by high fat diet and a low dose of streptozotocin injection. The effect of dietary supplementation of genistein on glycemic control and beta-cell mass and function was determined. Dietary intake of genistein (250 mg.kg(-1) diet) improved hyperglycemia, glucose tolerance, and blood insulin level in obese diabetic mice, whereas it did not affect body weight gain, food intake, fat deposit, plasma lipid profile, and peripheral insulin sensitivity. Genistein increased the number of insulin-positive beta-cell in islets, promoted islet beta-cell survival, and preserved islet mass. In conclusion, dietary intake of genistein could prevent T2D via a direct protective action on beta-cells without alteration of periphery insulin sensitivity.