Molecular targets for botanical compounds genistein and kaempferol to prevent diabetes

Abstract

Type 2 diabetes (T2D) is a result of chronic insulin resistance and loss of functional â‐cell mass. Thus, a method to simultaneously prevent insulin resistance and protect â‐cells could be a more effective strategy to prevent T2D. Here, we discovered that genistein, an isoflavone present in soybean, directly protects â‐cells from apoptosis ex vivo and promotes islet mass and ameliorates hyperglycemia in streptozotocin‐induced diabetic mice, while kaempferol, a flavonol isolated from gingko biloba, improves insulin sensitivity and glucose homeostasis in high fat diet‐fed mice. Notably, genistein in combination with kaempferol produces a potent additive effect on blood glycemic control in middle‐aged obese diabetic mice. We further found that genistein may protect against â‐cell apoptosis through the G‐protein coupled receptor GPR30‐mediated mechanism, leading to the activation of multiple cell survival pathways, while kaempferol increases energy metabolism, AMPKá activity, and Glut4 protein expression in skeletal muscle cells. These findings demonstrate a potential for using a combination of genistein and kaempferol to prevent diabetes by targeting two critical defects leading to T2D. This work was supported by grants from the ADA (7‐11‐BS‐84 to DL), the NCCAM of NIH (1R21AT004694 to D. Liu), and the Biodesign and Bioprocessing Research Center, College of Agriculture and Life Sciences, Virginia Tech.