Peptides From Adzuki Bean and Soybean Improved Insulin-AKT Signaling-Related Pathways in Healthy and Insulin-Resistant States in Human Liver Cells

The objectives were to determine the effect and mechanism of functional peptides identified from digested adzuki bean β-vignin and soybean β-conglycinin on insulin-AKT signaling and hepatic glucose uptake markers and to investigate the roles of these peptides in modulating the insulin-AKT signaling pathway in human liver cells in healthy and insulin-resistant states. Methods and Results: Adzuki bean β-vignin and soybean β-conglycinin proteins were isolated and digested using simulated gastrointestinal digestion. Peptide sequences (VP, PM, FNE, LLS, and IPA), in silico analysis and in vitro (cell-free and HepG2 cell-based) systems confirmed their safety and dipeptidyl peptidase IV (DPP IV) inhibitory capacity. IPA and VP showed high intestinal absorption and low toxicity, inhibited DPP IV (IPA IC₅₀, 7.86 µM; VP IC₅₀, 9.58 µM). Microarray results showed that VP (9.58 µM) stimulated the insulin signaling pathway in the healthy state. In healthy and insulin-resistant states, VP (9.58 µM) and IPA (7.86 µM) significantly increased (p < 0.05) protein expression of IRS-1, Akt-1, and Glut 2, suggesting their potential in modulating insulin signaling and hepatic glucose uptake. Peptides exhibited antidiabetic properties by stimulating insulin signaling. These in vitro findings support further investigation into their application in functional food ingredients targeting glucose metabolism.