Preparation, Characterization, and Mechanism of Hypoglycemic Action of a Goat Casein Peptide Delivery System Involving DPP-IV Inhibition and GLP-1 Release

This study aimed to formulate a carrier system to improve the oral bioaccessibility of goat casein peptides (GCAPS). Goat casein was hydrolyzed with papain and subsequently purified to obtain bioactive peptide fractions (GCAPS) with potent hypoglycemic activity. On this basis, spherical GCAPS-loaded nanocarrier systems were developed, including liposomes (GCAPS-LS) and niosomes (GCAPS-NS). Among them, GCAPS-NS exhibited higher encapsulation efficiency (94.98 ± 3.01%) and a smaller particle size (89.81 ± 8.97 nm) than GCAPS-LS. FT-IR analysis confirmed successful peptide encapsulation. Simulated gastrointestinal digestion experiments demonstrated that GCAPS-NS significantly improved GCAPS retention and DPP-IV inhibition. In vivo results from high-fat diet-induced (HFD) insulin-resistant mice demonstrated that GCAPS-NS effectively ameliorated metabolic abnormalities by including adiposity, enhancing GLP-1 levels and suppressing hsCRP expression, thereby contributing to improved glycemic homeostasis. Moreover, GCAPS-NS intervention resulted in a significant enrichment of <i>Akkermansia</i> and a reduced <i>Firmicutes</i>/<i>Bacteroidetes</i> ratio, suggesting its beneficial role in alleviating HFD gut dysbiosis. These findings indicated that goat casein peptides held great potential as a functional food for the management of type 2 diabetes.