Ameliorative effect of Polygonatum cyrtonema Hua polysaccharide on HFD/STZ-induced type 2 diabetes mice via improving gut microbiota imbalance and glucose metabolism disorder.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by insulin resistance and deficiency. Polysaccharides from Polygonatum cyrtonema Hua have garnered widespread attention for the prevention and management of metabolic diseases owing to their broad pharmacological activity. Therefore, this study aimed to investigate the effects and underlying mechanisms of the P. cyrtonema Hua polysaccharide component, PCP1, an agavin-type fructan with a molecular weight of 4650 Da, on T2DM mice. Mice were fed a high-fat, high-sugar diet and injected with a low-dose of streptozotocin to establish a T2DM model. During an 8-week intervention period, the mice were administered with different doses of PCP1 by gavage. Following, the biochemical, transcriptomic, and metabolomic analyses were performed. The results showed that PCP1 effectively improved insulin resistance, glycolipid metabolic disorders, oxidative stress, inflammatory responses, and liver injury in diabetic mice. Mechanistic studies revealed that PCP1 ameliorated gut microbiota dysbiosis, promoted the production of SCFAs, upregulated the expression of GPR43 in colon tissue, enhanced the secretion of GLP-1 and PYY, and activated the IRS1/PI3K/Akt signaling pathway in the liver. Further validation using NCI-H716 cells treated with the inhibitor GLPG0974 demonstrated that GLP-1 and PYY secretion were indirectly promoted by SCFAs through activating GPR43 receptor, but not entirely dependent on GPR43 pathway. In conclusion, this study indicated that PCP1 ameliorated T2DM probably through improving gut microbiota imbalance and glucose metabolism disorder, thereby establishing a theoretical foundation for the prebiotic development of P. cyrtonema Hua a polysaccharide.