Structural Characterization and Hypoglycemic Mechanism of Pumpkin Seed Polysaccharides

This study investigated three pumpkin seed polysaccharide fractions (PSP-1-1, PSP-1-2, and PSP-1-3) with molecular weights of 29,797 Da, 11,209 Da, and 4,346 Da, respectively, all containing both α- and β-glycosidic linkages. Structural analysis revealed arabinose, galactose, and glucose as predominant residues in PSP-1-1, while PSP-1-2 and PSP-1-3 additionally contained xylose, with all fractions sharing common structural units. All three fractions dose-dependently promoted GLP-1 secretion from L cells and upregulated sweet taste receptor pathway genes. The pooled fraction PSP-1s exhibited synergistic effects with higher gene expression than individual fractions and was therefore selected for in vivo studies. In diabetic mice, PSP-1s alleviated weight loss, reduced hyperphagia and polydipsia, lowered blood glucose, improved glucose tolerance and dyslipidemia, repaired pancreatic islets, and decreased GSP, insulin, and HOMA-IR while increasing QUICKI in a dose-dependent manner. PSP-1s enhanced GLP-1 secretion, elevated colonic SCFAs concentrations, and restructured gut microbiota by enriching beneficial SCFA-producing bacteria. Collectively, PSP-1s exerts hypoglycemic effects through dual mechanisms: remodeling gut microbiota to increase SCFA-stimulated GLP-1 secretion, and directly activating sweet taste receptors on L cells to enhance GLP-1 release, ultimately regulating blood glucose via the gut-brain GLP-1 signaling axis. These findings highlight PSP-1s as a promising candidate for type 2 diabetes management.