Hypoglycemic mechanism of Tegillarca granosa polysaccharides on type 2 diabetic mice by altering gut microbiota and regulating the PI3K-akt signaling pathwaye

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease threatening human health. We investigated the effects of Tegillarca granosa polysaccharide (TGP) and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin. TGP (5.1 × 10³ Da) was composed of mannose, glucosamine, rhamnose, glucuronic acid, galactosamine, glucose, galactose, xylose, and fucose. It could signif icantly alleviate weight loss, reduce fasting blood glucose levels, reverse dyslipidemia, reduce liver damage from oxidative stress, and improve insulin sensitivity. RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance. TGP increased the abundance of Allobaculum, Akkermansia, and Bifi dobacterium, restored the microbiota abundance in the intestinal tracts of mice with T2DM, and promoted short-chain fatty acid production. This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.