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
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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.
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Some algal peptides stimulate the release of GLP-1, a gut hormone that helps control blood sugar levels and promotes fullness after meals.
“Some algal peptides stimulate the release of GLP-1 (Glucagon-Like Peptide-1), a gut hormone that helps control blood sugar levels and promotes a feeling of fullness after meals [97].”
From Navigating the potential of algal peptides: health effects, market applications, and scientific challenges (2026) · cites this paper as [97]
The Results (Promotion of the incretin effect; page unavailable) show that several Palmaria palmata protein hydrolysates increased GLP-1 secretion in vitro. The Introduction identifies GLP-1 as a gut-derived hormone involved in the insulin response, and Materials and methods describes it among satiety hormones. The Discussion cautions that these were crude mixtures and that specific peptides responsible were not identified, so the claim that algal peptides themselves stimulate release goes beyond what was established. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPalmaria palmata protein hydrolysates elicited significant insulinotropic effects (p < 0.05-0.001), and their simulated digestion retained or even enhanced insulin secretion and GIP release.
“Palmaria palmata protein hydrolysates elicited significant insulinotropic effects (p < 0.05–0.001), and their simulated digestion retained or even enhanced insulin secretion and GIP release [97].”
From Navigating the potential of algal peptides: health effects, market applications, and scientific challenges (2026) · cites this paper as [97]
Simulated digestion of Palmaria palmata protein hydrolysates exhibited DPP-IV inhibitory activity.
“Additionally, simulated digestion of Palmaria palmata protein hydrolysates also exhibited DPP-IV inhibitory activity [97].”
From Navigating the potential of algal peptides: health effects, market applications, and scientific challenges (2026) · cites this paper as [97]
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- 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.
- Affiliations
- University of Ulster (GB)
- University of Limerick (IE)
- ORCID
- Venue
- European Journal of Nutrition
- Published
- 2021-06-03
- Volume
- 60
- Issue
- 8
- Pages
- 4439-4452
- ISSN
- 1436-6207 (ISSN-L)
- 1436-6215
- PMC
- PMC8572210
- OpenAlex
- W3164462872
- Cited by
- 45
- References
- 74
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 10 · 2023: 5 · 2022: 3 · 2021: 1
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- European Journal of Nutrition (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Limerick Institutional Repository (University of Limerick) (acceptedVersion, cc-by-nc-sa)
- University of Limerick Institutional Repository (University of Limerick) (acceptedVersion, other-oa)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Figshare (submittedVersion, cc-by-nc-sa)
- Ulster University Research Portal (Ulster University) (submittedVersion, other-oa)
- University of Limerick Institutional Repository (University of Limerick)
- Funders
- Department of Agriculture, Food and the Marine (11/F/063, 11/F064, 13/F536, 14/F873)
- Department of Education & Learning, Northern Ireland (PhD Studentship)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Hydrolysis and Bioactive Peptides
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
- Keywords
- Palmaria palmata, DPP-4 inhibition, incretin effect, GLP-1 secretion, GIP secretion, insulin secretion, insulinotropic effect, in vitro digestion, oral bioavailability, cAMP signaling, intracellular calcium, membrane potential, glucose tolerance, satiety, bromelain
- MeSH terms
- Animals, Blood Glucose, Diabetes Mellitus, Experimental, Gastric Inhibitory Polypeptide, Insulin, Protein Hydrolysates, Up-Regulation, Mice, Glucagon-Like Peptide 1, Incretins
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