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

Abstract

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-γ 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 β-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.