Insights into novel α-glucosidase (α-GLU) inhibitory peptides from sturgeon fish muscle protein based on in-silico and in-vitro investigation

Food-derived α-glucosidase (α-GLU) inhibitory peptides have emerged as promising natural agents for managing type 2 diabetes mellitus (T2DM) due to their favorable safety and bioactivity profiles. Food-derived α-glucosidase (α-GLU) inhibitory peptides have received considerable interest in managing type 2 diabetes mellitus (T2DM) due to their high safety. This study identifies high-activity α-glucosidase (α-GLU) inhibitory peptides from sturgeon fish muscle protein (SFMP) and investigates their mechanisms of action on α-GLU inhibition and enhancement of insulin-resistant HepG2 cells (IR-HepG2) through a systematic investigation. Moreover, two peptides, VLLQKNNDT (VT-9) and LSMQRAQEE (LE-9), exhibited significant α-GLU inhibitory activity and stability as confirmed by in vitro gastrointestinal digestion simulations. Molecular docking revealed that VT-9 and LE-9 interact with α-GLU active sites, induce conformational changes, and thus reduce α-GLU activity. Moreover, both peptides promoted glucose consumption and glycogen synthesis in IR-HepG2 cells, which improves insulin resistance through the modulation of insulin signaling pathways. Experimental validation confirms the hypoglycemic effects of these peptides, providing insights into SFMP development and its potential in anti-diabetic foods in managing T2DM.