Large-leaf yellow tea oligosaccharides alleviate T2DM by promoting GLP-1 secretion and regulating intestinal mucosal barrier.

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.