Peptide profiling of casein peptide reveals its anti-diabetic effects via DPP-IV inhibition and IRS1/PI3K/AKT signaling

) and crossed Caco-2 monolayers partly through endocytosis and PepT1-mediated transport. In HFD/STZ-induced T2DM mice, CNP improved glucose tolerance and insulin sensitivity, ameliorated dyslipidemia, attenuated tissue injury and systemic inflammation, and restored GLP-1/DPP-IV balance and IRS1/PI3K/AKT signaling. These findings identify CNP as a key food-derived bioactive peptide system that modulates T2DM through complementary effects on intestinal transport, incretin regulation, glucose-lipid homeostasis, inflammation, and insulin signaling, supporting its potential for development as a functional food ingredient for T2DM management.