A novel exploration of the extraction of sea cucumber glycoproteins and their potential mechanism in prediabetes intervention.

Prediabetes (PDM) represents an intermediate stage between normal glucose metabolism and diabetes mellitus (DM), with appropriate interventions capable of attenuating progression to DM. Marine-derived glycoproteins have received widespread attention for multiple activities and due to their lack of side effects, but sea cucumber glycoproteins (SCGP) and their hypoglycemic mechanisms remain unexplored. In this study, SCGP was investigated for its effects on the hepatic and intestinal glucose metabolism transport mechanisms by establishing a PDM mouse model through high-fat and high-sugar diet feeding. The results demonstrated that SCGP could restore fasting glucose and oral glucose tolerance to normal levels, improve postprandial glucose, insulin resistance and lipid levels, and enhance insulin sensitivity in PDM mice. Additionally, the results demonstrated that SCGP improved hepatic glucose metabolism by up-regulating the INSR/PI3K/AKT pathway, which could also alleviate insulin resistance. Moreover, SCGP promoted the intestinal barrier by upregulating zonula occludin and mucin 2, and it enhanced small intestine glucose transport and absorption by regulating the PLCβ2/PKCα/SGLT1-GLUT2 pathway. Furthermore, SCGP regulated the abundance of Lactobacillus, Roseburia and Faecalibaculum linked to DM at the genus level. Overall, this study demonstrated the potential of SCGP in intervening in hyperglycemia, preventing PDM from developing into DM, which provides a theoretical foundation for the development of natural functional products related to the intervention of PDM.