Multiple mechanisms of fucoidan degradation products in improving postprandial hyperglycemia.

Postprandial hyperglycemia remains a critical driver of diabetes progression. Fucoidan, a marine-derived sulfated polysaccharide with broad bioactivity, yields degradation products (FUDPs) that exhibit optimized physicochemical properties and superior hypoglycemic effects, though their antihyperglycemic mechanisms remain mechanistically underexplored. This study investigated hypoglycemic mechanisms of low/high-molecular-weight FUDPs (LMAF: <1.5 kDa; HMAF: 1.5-20 kDa) through digestive enzyme inhibition assays and insulin resistance mice model. The results demonstrated that FUDPs exhibited reversible inhibition of α-amylase/α-glucosidase via static quenching-mediated polarity modulation of Trp/Tyr residues, with HMAF additionally altering α-amylase secondary structures. In the in vivo experiments, HMAF synergistically enhanced insulin secretion and increased insulin sensitivity by upregulating gene expression of GLP-1 and GIP. Moreover, FUDPs controlled postprandial glucose elevation by downregulating gene expression in the PKCα/SGLT1/GLUT2 pathway. Overall, this study revealed FUDPs (<20 kDa) postprandial hyperglycemia regulation mechanisms and provided critical insights for establishing fucoidan structure-activity relationships and developing targeted hypoglycemic functional foods.