Peptides IPVP and LPIA Induce Insulin Secretion in a 2-Tiered Caco-2-STC-1/BRIN-BD11 Cell Model

The insulin release effects of two peptides, IPVP and LPIA, derived from a brewers’ spent grain (BSG) protein hydrolysate, were investigated using a two-tiered Caco-2 and STC-1 (apical: intestinal and enteroendocrine cells, respectively)/BRIN-BD11 (basolateral: pancreatic cells) cell model. Both peptides significantly enhanced insulin secretion in BRIN-BD11 cells (29.64 ± 3.30 and 28.30 ± 1.98 pM insulin for LPIA and IPVP, respectively) following their inclusion on the apical side. However, the direct exposure of BRIN-BD11 cells to peptides did not induce significant changes in insulin secretion, suggesting an indirect mode of action. LPIA significantly increased glucagon-like peptide-1 (GLP-1) levels (43.83 ± 9.25 pM), a known enhancer of insulin release, after 2 h of incubation during Caco-2 and STC-1 cell coculture. Additionally, IPVP and LPIA inhibited dipeptidyl peptidase-IV (DPP-IV) activity in vitro with IC₅₀values of 38.96 ± 1.26 μM and 31.20 ± 1.15 μM, respectively, and in situ using Caco-2 cells with IC₅₀values of 58.42 ± 0.45 μM and 59.01 ± 6.54 μM, respectively. The inhibition was via a noncompetitive mixed-type mechanism, and they resisted DPP-IV degradation. These findings highlight the therapeutic potential of IPVP and LPIA in type 2 diabetes management via GLP-1- and DPP-IV-related pathways and warrant further molecular and clinical-level investigations.