Genistein in Combination with Sulforaphane for the Treatment of Type 2 Diabetes

Insulin resistance and loss of functional beta-cell mass are hallmarks for the pathogenesis of type 2 diabetes (T2D). Therefore, the search for agents that simultaneously reverse these two defects could be a more effective strategy to treat T2D. We recently reported that dietary provision of genistein (0.5 g/kg diet) preserved pancreatic b-cell mass and ameliorated hyperglycemia in diabetic mice. Here, we found that sulforaphane (0.25 g/kg diet), a small molecule derived from cruciferous vegetables prevented insulin resistance in diet-induced obese mice. Notably, oral administration of genistein in combination with sulforaphane completely normalized hyperglycemia and insulin sensitivity in middle-aged obese diabetic mice. Ex vivo, genistein directly promoted viability of cultured human and mouse islets chronically exposed to palmitate (0.5 mM) and high glucose (HG, 20 mM). On molecular levels, genistein activates GPR30, which subsequently induces the Gαs/cAMP/PKA/CREB pathway essential for promoting beta ...