Amelioration of\nType 2 Diabetes Mellitus Using Rapeseed\n(<i>Brassica napus</i>)‑Derived Peptides through\nStimulating Calcium-Sensing Receptor: Effects on Glucagon-Like Peptide‑1\nSecretion and Hepatic Lipid Metabolism

The\npotential of rapeseed-derived peptides (RDPs) in the amelioration\nof type 2 diabetes mellitus (T2DM) has been hypothesized. However,\nthe mechanisms of the intestinal endocrine hormones activated by RDPs\nhave not been fully understood. This study aimed to explore the amelioration\nof T2DM and associated hepatic lipid metabolism disorders using RDPs\nby affecting glucagon-like peptide-1 (GLP-1) secretion. Eight RDPs\nwere prepared by different stepwise enzymatic hydrolysis, wherein\nRCPP-3 (sequential using alcalase/flavourzyme) and RNPP-1 (sequential\nusing alcalase/trypsin) maintained the normal blood glucose level,\nsignificantly increased the body weight (27.17 ± 0.19%) in T2DM\nmice compared to the positive group (<i>p</i> < 0.05).\nWestern blotting and immunofluorescence experiments indicated that\nRCPP-3 and RNPP-1 regulated the intestinal endocrine hormones GLP-1\nsecretion through the calcium-sensing receptor (CaSR). Additionally,\nthe PI3K-Akt pathway was significantly activated by GLP-1, leading\nto marked improvements in hepatic lipid parameters (TC, TG, LDL-c,\nand HDL-c) and mitigated fat accumulation (<i>p</i> <\n0.05). Notably, the stimulating effect of RCPP-3 on GLP-1 was 10.05%\n± 0.71% higher than RNPP-1. G2-R3, a fraction separated from\nRCPP-3, which contained 14 peptides with the best capacity to stimulate\nGLP-1 secretion, was identified using HPLC-QTOF-MS/MS. This study\nsuggests the potential of RDPs as novel functional food supplements\nfor ameliorating T2DM.