Isoflavonoids and peptides from meju, long-term fermented soybeans, increase insulin sensitivity and exert insulinotropic effects in vitro

Objective: Although soybeans have been shown to alleviate metabolic syndromes, fermented soybeans may have even greater effects. We investigated the antidiabetic effects of meju, a soy food that is fermented up to 2 mo, and the mechanism by which it exerts its effects. Methods: Meju was prepared by a traditional fermentation process: soybeans were fermented outdoors for 20 or 60 d. Methanol (M-60) and water (W-60) extracts from meju that had fermented for 60 d contained mostly isoflavonoid aglycones and small peptides, respectively, as opposed to mostly glycosylated isoflavonoids and proteins in the original soybeans. Results: Daidzein, M-60, and W-60 had better insulin-sensitizing actions by activating peroxisome proliferator-activated receptor-gamma in 3T3-L1 adipocytes than did unfermented soybeans. In addition, Min6 insulinoma cells treated with genistein, M-60, and W-60 had greater glucose-stimulated insulin secretion capacity and greater beta-cell viability than those treated with unfermented soybeans. This improvement was associated with insulin/insulin-like growth factor-1 signaling that was activated by the tyrosine phosphorylation of insulin receptor substrate-2 and serine phosphorylation of Akt, and this in turn increased pancreatic and duodenal homeobox-1 expression. Furthermore, genistein, daidzein, and M-60 stimulated glucagon-like peptide-1 secretion in enteroendocrine NCI-H716 cells, which generated insulinotropic actions. Conclusion: The compositional changes in isoflavonoids and peptides that occurred during a longer fermentation period, without the use of salt, enhanced the antidiabetic effect of soybeans. (C) 2011 Elsevier Inc. All rights reserved.