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

• Published in: European journal of nutrition Vol. 60; no. 8; pp. 4439 - 4452
• Main Authors: McLaughlin, C. M., Harnedy-Rothwell, P. A., Lafferty, R. A., Sharkey, S., Parthsarathy, V., Allsopp, P. J., McSorley, E. M., FitzGerald, R. J., O’Harte, F. P. M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2021; Springer Nature B.V
• Subjects: Animals; Antidiabetics; Bioavailability; Biological activity; Blood Glucose; Calcium (intracellular); Chemistry; Chemistry and Materials Science; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose tolerance; Hydrolysates; Incretins; Insulin; Insulin - metabolism; Insulin secretion; Intracellular; Membrane potential; Mice; Nutrition; Original Contribution; Palmaria palmata; Protein Hydrolysates; Proteins; Satiety; Seaweeds; Secretion; Streptozocin; Subtilisin; Up-Regulation; Type 2 diabetes; Dulse; Protein hydrolysate; Dipeptidylpeptidase-4; Antidiabetic; Incretin secretion; Palmaria palmata
• DOI: 10.1007/s00394-021-02583-3
• ISSN: 1436-6207; 1436-6215

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 effect 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, respectively. 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 effects ( 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 confirmed 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.