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Here the PPPH, was compared to alternative Alcalase, bromelain and Promod-derived hydrolysates and an unhydrolysed control. All PPPH\u2019s underwent simulated gastrointestinal digestion (SGID) to establish oral bioavailability. PPPH\u2019s 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>PPPH\u2019s (0.02\u20132.5\u00a0mg\/ml) elicited varying insulinotropic effects (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05\u20130.001). SGID of the unhydrolysed protein control, bromelain and Promod PPPH\u2019s 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\u2019s and SGID counterparts (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05\u20130.001). PPPH\u2019s were shown to directly influence the incretin effect via upregulated GLP-1 and GIP (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01\u20130.001) secretion in vitro, largely retained after SGID. Alcalase\/Flavourzyme PPPH produced the greatest elevation in cAMP (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, 1.7-fold), which was fully retained post-SGID. This hydrolysate elicited elevations in intracellular calcium (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and membrane potential (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). In acute in vivo settings, Alcalase\/Flavourzyme PPPH improved glucose tolerance (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01\u20130.001) and satiety (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05\u20130.001).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Bioavailable PPPH peptides may be useful for the management of T2DM and obesity.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00394-021-02583-3","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T12:03:21Z","timestamp":1622721801000},"page":"4439-4452","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Macroalgal protein hydrolysates from Palmaria palmata influence the \u2018incretin effect\u2019 in vitro via DPP-4 inhibition and upregulation of insulin, GLP-1 and GIP secretion"],"prefix":"10.1007","volume":"60","author":[{"given":"C. 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