Macroalgal protein hydrolysates from palmaria palmata influence the ‘incretin effect’ in vitro via DPP‑4 inhibition and upregulation of insulin, GLP‑1 and GIP secretion

Purpose This study investigated metabolic benefits of protein hydrolysates from the macroalgae Palmaria palmata, previously shown to inhibit dipeptidylpeptidase-4 (DPP-4) activity in vitro. Methods Previously, Alcalase/Flavourzyme-produced P. palmata protein hydrolysate (PPPH) improved glycaemia and insulin production in streptozotocin-induced diabetic mice. Here the PPPH, was compared to alternative Alcalase, bromelain and Promod-derived hydrolysates and an unhydrolysed control. All PPPH’s underwent simulated gastrointestinal digestion (SGID) to establish oral bioavailability. PPPH’s and their SGID counterparts were tested in pancreatic, clonal BRIN-BD11 cells to assess their insulinotropic efect and associated intracellular mechanisms. PPPH actions on the incretin effect were assessed via measurement of DPP-4 activity, coupled with GLP-1 and GIP release from GLUTag and STC-1 cells, respec tively. Acute in vivo effects of Alcalase/Flavourzyme PPPH administration on glucose tolerance and satiety were assessed in overnight-fasted mice. Results PPPH’s (0.02–2.5 mg/ml) elicited varying insulinotropic efects (p<0.05–0.001). SGID of the unhydrolysed protein control, bromelain and Promod PPPH’s retained, or improved, bioactivity regarding insulin secretion, DPP-4 inhibition and GIP release. Insulinotropic effects were retained for all SGID-hydrolysates at higher PPPH concentrations. DPP-4 inhibitory effects were confrmed for all PPPH’s and SGID counterparts (p<0.05–0.001). PPPH’s were shown to directly influence the incretin effect via upregulated GLP-1 and GIP (p<0.01–0.001) secretion in vitro, largely retained after SGID. Alcalase/Flavourzyme PPPH produced the greatest elevation in cAMP (p<0.001, 1.7-fold), which was fully retained post-SGID. This hydrolysate elicited elevations in intracellular calcium (p<0.01) and membrane potential (p<0.001). In acute in vivo settings, Alcalase/Flavourzyme PPPH improved glucose tolerance (p<0.01–0.001) and satiety (p<0.05–0.001). Conclusion Bioavailable PPPH peptides may be useful for the management of T2DM and obesity.