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Genistein in Combination with Sulforaphane for the Treatment of Type 2 Diabetes
Author(s) -
Liu Dongmin,
Wang Aihua,
Liu Jing,
Alkhalidy Hana,
Zhen Wei,
Moore William
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.646.51
Subject(s) - sulforaphane , genistein , type 2 diabetes , insulin resistance , endocrinology , medicine , diabetes mellitus , insulin , pharmacology , chemistry , phytoestrogens , biochemistry , estrogen
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 cell survival. Consistently, oral administration of genistein (50 mg/kg body weight) mitigated STZ‐induced hyperglycemia in WT but not in GPR30 KO diabetic mice. Moreover, we show that sulforaphane promoted mitochondrial function, enhanced pyruvate and fatty acid oxidation, and increased glucose uptake in primary human muscle cells. These results demonstrate for the first time that the combination of phytonutrient genistein and sulforaphane with complimentary mechanisms of actions may have considerable potential for preventing and treating T2D. Support or Funding Information The work was supported by grants from NCCIH of NIH (1R01AT007077, 1R01AT007566) and the American Diabetes Association Diabetes Basic Research Award (7‐11‐BS‐84).