Abstract
PurposeThis study investigated metabolic benefits of protein hydrolysates from the macroalgae Palmaria palmata, previously shown to inhibit dipeptidylpeptidase-4 (DPP-4) activity in vitro.MethodsPreviously, 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.ResultsPPPH’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).ConclusionBioavailable PPPH peptides may be useful for the management of T2DM and obesity.
Highlights
Type 2 diabetes mellitus (T2DM) is a metabolic disorder of complex aetiology characterised by a deficiency, and/ or dysfunction of endogenous insulin and glucagon production [1]
Insulin secretion was determined over a 20 min co-incubation with P. palmata protein hydrolysate (PPPH) supplemented glucose
Baseline insulin secretion was established utilising Krebs Ringer bicarbonate buffer (KRBB) buffer supplemented with basal 5.6 mM or elevated 16.7 mM glucose
Summary
Type 2 diabetes mellitus (T2DM) is a metabolic disorder of complex aetiology characterised by a deficiency, and/ or dysfunction of endogenous insulin and glucagon production [1]. Best-estimates state that there are around 463 million adults globally living with diabetes, projected to rise to 700 million by 2045 [4], with T2DM representing ~ 90% of cases. The economic burden of diabetes on global healthcare systems is considerable, with a minimum of $760 billion USD attributed to spending on the disease in 2019, equating to 10% of global adult healthcare costs [4]. An important factor in this spending arises from costs amassed from treatment of microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular (coronary artery disease, stroke, and peripheral vascular disease) complications [5]. Preventative strategies, coupled with earlier diagnosis and novel treatments, have the potential to reduce the occurrence of these complications [6]
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