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 4346 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 were associated with dose-dependent increases in GLP-1 secretion from L cells and with upregulation of genes in the sweet taste receptor pathway. The pooled fraction PSP-1s showed higher gene expression than individual fractions and was therefore selected for in vivo studies. In diabetic mice, PSP-1s intervention alleviated weight loss, reduced hyperphagia and polydipsia, lowered blood glucose, improved glucose tolerance and dyslipidemia, and decreased GSP, insulin, and HOMA-IR while increasing QUICKI. Qualitative histological observations suggested less pronounced pancreatic islet abnormalities following PSP-1s intervention. PSP-1s increased serum GLP-1 concentrations and colonic SCFA concentrations and altered gut microbiota composition. Collectively, the hypoglycemic effects of PSP-1s were accompanied by changes in serum GLP-1, colonic SCFAs, gut microbiota composition, and hypothalamic GLP-1R and appetite-related gene expression. Together with the cellular findings, these observations suggest potential mechanisms involving sweet taste receptor-related signaling and microbiota-associated GLP-1 regulation. However, pathway activation and the causal contribution of gut–brain signaling remain to be established. These findings support further investigation of PSP-1s as a functional food ingredient with potential glucose-regulating activity.