A mechanistic study of how a lipid-rich Eupolyphaga sinensis Walker molt extract attenuates starch digestion and improves glucose homeostasis.

Edible insect by-products are increasingly recognized as sustainable sources of functional ingredients for the development of novel food products; however, their potential to modulate starch digestion remains underexplored. Compared with many plant-derived preparations dominated by phenolics, insect-derived extracts may offer a broader combination of lipid-derived metabolites, fatty acids, and phenolic compounds for coordinated regulation of digestive enzymes and glucose metabolism. This study investigated an ethyl acetate extract (EAE) from Eupolyphaga sinensis Walker molt for attenuating starch digestion and improve glycemic regulation. Among five sequential solvent extracts, EAE exhibited the strongest α-amylase and α-glucosidase inhibition, low cytotoxicity, and enhanced glucose uptake and glycogen synthesis in insulin-resistant HepG2 cells. Chemical profiling putatively annotated 189 compounds, mainly lipid-related metabolites, phenolic/flavonoid derivatives, and free fatty acids. Linoleic and oleic acids were the predominant fatty acids, whereas gallic acid and caffeic acid were the major phenolic acids. Mechanistic analyses showed EAE reversibly and competitively inhibited α-glucosidase, while metabolomics and molecular docking indicated contributions from lipid-derived metabolites and phenolic acids. EAE significantly reduced starch hydrolysis, increased resistant starch content, and lowered hydrolysis index and estimated glycemic index of different crystalline starch types (P < 0.05), partly by reducing substrate accessibility. In high-fat diet/streptozotocin-induced type 2 diabetes mice, EAE reduced fasting blood glucose, and improved glucose tolerance and insulin responsiveness without increasing serum alanine aminotransferase or aspartate aminotransferase levels in non-diabetic mice. These findings identify EAE as a promising edible insect-derived ingredient useful for developing low-glycemic starch-based foods.