Dietary protein source Enzyme used to produce peptides Peptide sequence or molecular weight Object IC50 /EC50 values Activity/mechanisms of action Reference Rice bran Umamizyme G and bioprase SP Dipeptides LP and IP DPP-IV inhibition assay DPP-IV IC50 Peptides sowed strong DPP-IV inhibition activity [130 ] Egg white albumin Alcalase KLPGF α -Glucosidase and α -amylase inhibitory assaysα -Glucosidase inhibitory IC50 α -amylase inhibitory IC50 120 μ MKLPGF exhibited strong antidiabetic potential by inhibiting α -glucosidase and α -amylase activities [66 ] Casein Prolyl oligopeptidase FLQP DPP-IV inhibition assay DPP-IV IC50 FLQP exhibited DPP-IV inhibition activity [70 ] Bovine and porcine meat proteins Papain and pepsin PPL DPP-IV inhibition assay DPP-IV IC50 390.14 μ M Peptides showed DPP-IV inhibition [131 ] Porcine skin Alcalase and flavourzyme — Streptozotocin-induced diabetic rats — Peptides improved glucose tolerance and inhibited DPP-IV activity and enhanced GLP-1 and the insulin level [132 ] Egg yolk Proteinase from Asian pumpkin LAPSLPGKPKPD DPP-IV and α -glucosidase assays DPP-IV IC50 361.5 μ mol/L and α -glucosidase IC50 1065.6 μ mol/L Peptides showed DPP-IV and α -glucosidase inhibitory activities [67 ] Halibut and tilapia skin gelatin Flavourzyme SPGSSGPQGFTG,GPVGPAGNPGANGLN, PPGPTGPRGQPGNIGF, IPGDPGPPGPPGP, LPGERGRPGAPGP, and GPKGDRGLPGPPGRDGM Streptozotocin-induced diabetic rats — Peptides improved glucose tolerance through DPP-IV inhibition and GLP-1 secretion enhancement [73 ] Styela clava Protamex — Patients with diabetes — Peptides exhibited a decreased hemoglobin A1c and plasma insulin levels [78 ] Black bean Alcalase AKSPLF, LSKSVL, FEELN, and PHL Caco-2 cell and rats — Peptides showed antidiabetic effects by blocking GLUT2 and SGLT1 and reduced glucose absorption and postprandial glucose and blood glucose [133 ] Wheat Bacterial protease 770–77740 Da GLUTag cells and rats — Peptides improved hyperglycemia via activating GLP-1 secretion via stimulation of the calmodulin-dependent kinase II pathway mediated by G protein-coupled receptor family C group 6 subtype A [134 ] Atlantic cod (Gadus morhua ) meat Protamex <2000 Da 41 healthy individuals — Peptides decreased the postprandial insulin [77 ] Oat globulin Trypsin OGb, LQAFEPLR, and EFLLAGNNK Caco-2 cell DPP-IV IC50 OGb 188.1 μ g/mL and LQAFEPLR IC50 141.7 μ M Peptides showed potent inhibition on DPP4 and α -glucosidase activity and reduced DPP4 protein expression and upregulated the expressions of α -glucosidase, GLUT2, and GLUT5 [135 ] Milk whey protein Protease <5000 Da 21 prediabetic humans — Peptides (1400 or 2800 mg/kg BW) decreased under glucose curve and showed a minor insulinotropic and reduced HbA1c [76 ] Egg white Thermolysin and pepsin IRW TNF-α -treated L6 rat skeletal muscle cells — IRW reduced glucose uptake and enhanced insulin receptor activation and improved insulin sensitivity by inhibiting p38 and JNK1/2 activation [23 ] Boarfish (Capros aper ) protein Alcalase and flavourzyme <2 kDa BRIN-BD11 and GLUTag cells and mice DPP-IV inhibitory activity IC50 1.18 mg/mL Peptides increased insulin secretion and inhibited DPP-IV activity. Peptides increased insulin levels and reduced glucose concentration [72 ] Blue whiting (Micromesistius poutassou ) muscle protein Alcalase and flavourzyme <5 kDa GLUTag cells, BRIN-BD11 cells, 3T3-L1 adipocytes, DPP-IV assay, and mice DPP-IV inhibitory activity IC50 Peptides showed being antidiabetic via DPP-IV inhibitory activity, increasing insulin-stimulated glucose, stimulating insulin secretion and GLP-1, and decreasing glucose [71 ] Potato protein Alcalase DIKTNKPVIF Diabetic mice — Peptides showed antidiabetic effects via regulation of blood glucose, plasma total glycerol, total cholesterol, insulin, and HbA1c [6 ] Spirulina platensis — GVPMPNK, RNPFVFAPTLLTVAAR, and LRSELAAWSR α -Amylase, α -glucosidase, and DPP-IV assayα -Amylase IC50 313.6 μ g/mL, α -glucosidase IC50 134.2 μ g/mL, and DPP-IV IC50 167.3 μ g/mLLRSELAAWSR exhibited strong inhibitory activity on α -amylase, α -glucosidase, and DPP-IV [68 ] Beans (Phaseolus vulgaris L.) Pepsin and pancreatin <3 kDa Wistar rats and mice and in vitro assays α -Amylase 16.9–89.1% and α -glucosidase inhibition 34.4–89.2%Fractions inhibited α -amylase and α -glucosidase. Fractions showed both hypoglycemic and antihyperglycemic activities [136 ] Soy protein Papain, trypsin, and alkaline proteinase LLPLPVL, SWLRL, and WLRL α -Glucosidase inhibitory assayα -Glucosidase IC50 162.2–237.4 μ mol/LPeptides showed strong α -glucosidase inhibitory activity [63 ] Sea cucumber (Holothuria nobilis ) Mixture of papain and protamex 203–1907 Da Type II diabetic rats induced by streptozotocin — Peptides (200 and 400 mg/kg BW) decreased fasting blood glucose. Peptides showed antidiabetic effects by increasing the expressions of PI3K, p-Akt, p-GSK-3β , and GLUT2/4 signaling pathways and decreasing the expression of p-IRS1 [73 ] Largemouth bass (Micropterus salmoides ) Pepsin, trypsin, and chymotrypsin ICY DPP-IV inhibitory assay DPP-IV IC50 0.73 mM ICY had strong DPP4 inhibitory activities [137 ] Zebra blenny (Salaria basilisca ) protein Crude alkaline protease extract from zebra blenny >30 kDa DPP-IV inhibitory assay DPP-IV IC50 71 μ g/mL Fraction showed α -amylase inhibitory activity [64 ] Walnut (Juglans mandshurica Maxim) Alcalase LPLLR Hepatic HepG2 cells and in vitro assays Inhibiting α -glucosidase 50.12% and α -amylase 39.08% at 2000 μ M LPLLR inhibited α -glucosidase and α -amylase and improved hepatic insulin resistance via enhancing glycogen synthesis and glucose uptake and reduced gluconeogenesis via activating the IRS-1/PI3K/Akt and AMPK pathways [75 ] Quinoa protein Bromelain, chymotrypsin, and Pronase E QHPHGLGALCAAPPST α -Glucosidase and DPP-IV inhibitory assaysDPP-IV IC50 0.72–1.12 mg/mL and α -glucosidase IC50 1.0–1.45 mg/mL Peptides showed antidiabetic effects by inhibiting DPP-IV and α -glucosidase [62 ] Corn germ protein Alcalase, trypsin, and flavourzyme <2–10 kDa In vitro assays Inhibiting α -amylase 71.3%, α -glucosidase 37.1%, and DPP-IV 45.9% Peptides showed strong α -amylase, α -glucosidase, and DPP-IV inhibition [61 ] Sea cucumber (Stichopus japonicus ) Pepsin, trypsin, and chymotrypsin <3 kDa 3T3-L1 and Hep G2 cells DPP-IV IC50 0.51–0.52 mg/mL Peptides improved glucose uptake and DPP-IV inhibitory activity [7 ] α -Lactalbumin-rich whey proteinsTrypsin LDQWLCEKL DPP-IV inhibitory activity DPP-IV inhibition IC50 131 μ M LDQWLCEKL exhibited DPP-IV inhibition with a noncompetition [138 ] Palmaria palmata Alcalase and flavourzyme <1–5 kDa Streptozotocin-induced diabetic mice — Peptides showed antidiabetic effects by reducing blood glucose and increasing insulin and improved terminal oral glucose tolerance and fasting blood glucose [139 ] Atlantic salmon (Salmo salar ) skin Trypsin LDKVFR DPP-IV inhibitory activity assay DPP-IV inhibition IC50 128.7 μ M LDKVFR showed DPP-IV inhibition [14 ] Millet proteins Papain NDWHTGPLS and TYPHQQPPILT DPP-IV inhibition assay DPP-IV inhibition 75.72% Peptides inhibited DPP-IV and occupied DPP-IV active center (S1 and S2 subsites) via H-bond and [21 ]
