Collagen peptides alleviate hyperglycemia in mice by modulating insulin resistance, glucose metabolism and gut microbiota.

In vitro studies have demonstrated that collagen peptides (CP) inhibit the activity of dipeptidyl peptidase-IV. However, the relationship between the AMPK-mediated insulin signaling pathway and gut microbiota modulation in Type 2 Diabetes Mellitus (T2DM) remains underexplored. Current research investigated the hypoglycemic mechanisms associated with CP intervention in a T2DM mouse model induced by a high-fat diet and streptozotocin (STZ). The findings revealed that administering CP (400 mg/kg/day) for 4 weeks significantly eased symptoms such as polydipsia, polyphagia, weight loss, and organ damage in diabetic mice. Following CP intervention, diabetic mice exhibited notable reductions in blood glucose and lipid levels, as well as decreased abundance ratios of Firmicutes and Bacteroides, whereas increased short-chain fatty acid concentration in the gut microbiota and the serum GLP-1 level, accompanied by a substantial decrease in the serum insulin resistance index. Furthermore, in the livers of mice post-CP intervention, there was an upregulation of IRS1, the increase of p-AMPK/AMPK and p-GSK3β/GSK3β (P < 0.01), coupled with downregulation of PEPCK and FoxO1 expression (P < 0.05), thereby facilitating glycogen synthesis, regulation of insulin sensitivity, and inhibition of glucose production. These results provide foundational insights into the potential of collagen peptide intervention in managing and preventing T2DM.