BACKGROUND: Glucagon-like peptide-1 (GLP-1), a key incretin produced by intestinal L-cells, plays a vital role in glucose and intestinal homeostasis during type 2 diabetes mellitus (T2DM) management. Large-leaf yellow tea polysaccharide (LYP) exhibits hypoglycemic effects, yet the structural features of LYP-derived bioactive oligosaccharides and their potential effects and mechanisms in promoting GLP-1 secretion remain unclear.
PURPOSE: This study aimed to isolate an active oligosaccharide from LYP and explore its effects and underlying mechanisms on GLP-1 secretion and intestinal homeostasis in T2DM.
METHODS: An oligosaccharide (ELYP) was obtained from enzymatic degradation of LYP guided by activity evaluation. Its structure was characterized, and in situ intestinal perfusion was used to assess GLP-1 secretion in mice. Molecular mechanisms were explored in T2DM mice and STC-1 cells. Intestinal microorganisms and metabolites, intestinal barrier integrity, as well as immunocytes profiles were analyzed.
RESULTS: ELYP primarily consists of 1,4-linked β-GalpA and 1,4-linked β-Glcp, with degrees of polymerization between 3 to 7. It significantly increased plasma GLP-1 levels and upregulated genes related to GLP-1 synthesis, processing, and release synthesis and secretion. ELYP also restored intestinal barrier function by enhancing tight-junction proteins and goblet cell numbers, enriching beneficial gut microbiota and SCFAs composition, and promoting a transition of macrophages and T lymphocytes to an anti-inflammatory phenotype.
CONCLUSION: ELYP effectively ameliorates T2DM by potently stimulating GLP-1 secretion and restoring intestinal homeostasis. This study not only identifies ELYP as a promising natural product for T2DM management but also provides new insights into the mechanism of tea-derived oligosaccharides.
