TY - JOUR
T1 - Utilisation of the isobole methodology to study dietary peptide-drug and peptide-peptide interactive effects on dipeptidyl peptidase IV (DPP-IV) inhibition
AU - Nongonierma, Alice B.
AU - Fitzgerald, Richard J.
N1 - Publisher Copyright:
© The Royal Society of Chemistry 2015.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Inhibition of dipeptidyl peptidase-IV (DPP-IV) is used as a means to regulate post-prandial serum glucose in type 2 diabetics. The effect of drug (Sitagliptin®)/peptide and binary peptide mixtures on DPP-IV inhibition was studied using an isobole approach. Five peptides (Ile-Pro-Ile-Gln-Tyr, Trp-Lys, Trp-Pro, Trp-Arg and Trp-Leu), having DPP-IV half maximum inhibitory concentration values (IC50) < 60 μM and reported to act through different inhibition mechanisms, were investigated. The dose response relationship of Sitagliptin:peptide (1:0, 0:1, 1:852, 1:426 and 1:1704 on a molar basis) and binary Ile-Pro-Ile-Gln-Tyr:peptide (1:0, 0:1, 1:1, 1:2 and 2:1 on a molar basis) mixtures for DPP-IV inhibition was characterised. Isobolographic analysis showed, in most instances, an additive effect on DPP-IV inhibition. However, a synergistic effect was observed with two Sitagliptin:Ile-Pro-Ile-Gln-Tyr (1:426 and 1:852) mixtures and an antagonistic effect was seen with one Sitagliptin:Trp-Pro (1:852) mixture, and three binary peptide mixtures (Ile-Pro-Ile-Gln-Tyr:Trp-Lys (1:1 and 2:1) and Ile-Pro-Ile-Gln-Tyr:Trp-Leu (1:2)). The results show that Sitagliptin and food protein-derived peptides can interact, thereby enhancing overall DPP-IV inhibition. Combination of Sitagliptin with food protein-derived peptides may help in reducing drug dosage and possible associated side-effects.
AB - Inhibition of dipeptidyl peptidase-IV (DPP-IV) is used as a means to regulate post-prandial serum glucose in type 2 diabetics. The effect of drug (Sitagliptin®)/peptide and binary peptide mixtures on DPP-IV inhibition was studied using an isobole approach. Five peptides (Ile-Pro-Ile-Gln-Tyr, Trp-Lys, Trp-Pro, Trp-Arg and Trp-Leu), having DPP-IV half maximum inhibitory concentration values (IC50) < 60 μM and reported to act through different inhibition mechanisms, were investigated. The dose response relationship of Sitagliptin:peptide (1:0, 0:1, 1:852, 1:426 and 1:1704 on a molar basis) and binary Ile-Pro-Ile-Gln-Tyr:peptide (1:0, 0:1, 1:1, 1:2 and 2:1 on a molar basis) mixtures for DPP-IV inhibition was characterised. Isobolographic analysis showed, in most instances, an additive effect on DPP-IV inhibition. However, a synergistic effect was observed with two Sitagliptin:Ile-Pro-Ile-Gln-Tyr (1:426 and 1:852) mixtures and an antagonistic effect was seen with one Sitagliptin:Trp-Pro (1:852) mixture, and three binary peptide mixtures (Ile-Pro-Ile-Gln-Tyr:Trp-Lys (1:1 and 2:1) and Ile-Pro-Ile-Gln-Tyr:Trp-Leu (1:2)). The results show that Sitagliptin and food protein-derived peptides can interact, thereby enhancing overall DPP-IV inhibition. Combination of Sitagliptin with food protein-derived peptides may help in reducing drug dosage and possible associated side-effects.
UR - http://www.scopus.com/inward/record.url?scp=84928102730&partnerID=8YFLogxK
U2 - 10.1039/c4fo00883a
DO - 10.1039/c4fo00883a
M3 - Article
C2 - 25477187
AN - SCOPUS:84928102730
SN - 2042-6496
VL - 6
SP - 313
EP - 320
JO - Food and Function
JF - Food and Function
IS - 1
ER -