Inhibition of carbohydrate digestive enzymes is a key focus across diverse fields, given the prominence of α-glucosidase inhibitors as preferred oral hypoglycaemic drugs for diabetes treatment. β-conglycinin is the most abundant functional protein in soy; however, it is unclear whether the peptides produced after its gastrointestinal digestion exhibit α-glucosidase inhibitory properties. Therefore, we examined the α-glucosidase inhibitory potential of soy peptides. Specifically, β-conglycinin was subjected to simulated gastrointestinal digestion by enzymatically cleaving it into 95 peptides with gastric, pancreatic and chymotrypsin enzymes. Eight soybean peptides were selected based on their predicted activity; absorption, distribution, metabolism, excretion and toxicity score; and molecular docking analysis. The results indicated that hydrogen bonding and electrostatic interactions play important roles in inhibiting α-glucosidase, with the tripeptide SGR exhibiting the greatest inhibitory effect (IC50 = 10.57 μg/mL). In vitro studies revealed that SGR markedly improved glucose metabolism disorders in insulin-resistant HepG2 cells without affecting cell viability. Animal experiments revealed that SGR significantly improved blood glucose and decreased maltase activity in type 2 diabetic zebrafish larvae, but it did not result in the death of zebrafish larvae. Transcriptomic analysis revealed that SGR exerts its anti-diabetic and hypoglycaemic effects by attenuating the expression of several genes, including Slc2a1, Hsp70, Cpt2, Serpinf1, Sfrp2 and Ggt1a. These results suggest that SGR is a potential food-borne bioactive peptide for managing diabetes.
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