Whey proteins as source of dipeptidyl dipeptidase IV (dipeptidyl peptidase-4) inhibitors

Tulipano, Giovanni; Sibilia, V.; Caroli, Anna; Cocchi, Daniela

doi:10.1016/j.peptides.2011.01.002

Cited by 177 publications

(134 citation statements)

References 18 publications

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“…Leu-Pro-Gln-Asn-Ile-Pro-Pro-Leu 46 (63) Leu-Pro-Gln-Asn-Ile-Pro-Pro 160 Pro-Gln-Asn-Ile-Pro-Pro-Leu 1500 Leu-Pro-Gln Val-Ala-Gly-Thr-Trp-Tyr 174 (64) β-lactoglobulin Ile-Pro-Ala 49 (65) β-lactoglobulin Ile-Pro-Ala-Val-Phe 45 (66) Ile-Pro-Ala-Val-Phe-Lys 143 Val-Leu-Val-Leu-Asp-Thr-Asp-Tyr-Lys 424 Thr-Pro-Glu-Val-Asp-Asp-Glu-Ala-Leu-Glu-Lys 320…”

Section: Gouda Cheeseunclassified

“…Each individual WP has different physicochemical properties, which can be modified by enzymatic hydrolysis and hydrolysis of WP has been shown to release DPP-IV inhibitory peptides (13,(64)(65)(66) . Digestion of WP with pepsin and pancreatin generated peptides with DPP-IV inhibitory activity and peptic digestion produced the most potent hydrolysate with an IC 50 value of 0·075 mg/ml.…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

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Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory peptides for the management of type 2 diabetes

2013

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The prevalence of type 2 diabetes mellitus (T2DM) is increasing and it is estimated that by 2030 approximately 366 million people will be diagnosed with this condition. The use of dipeptidyl peptidase IV (DPP-IV) inhibitors is an emerging strategy for the treatment of T2DM. DPP-IV is a ubiquitous aminodipeptidase that cleaves incretins such as glucagon like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), resulting in a loss in their insulinotropic activity. Synthetic DPP-IV drug inhibitors are being used to increase the half-life of the active GLP-1 and GIP. Dietary intervention is accepted as a key component in the prevention and management of T2DM. Therefore, identification of natural food protein-derived DPP-IV inhibitors is desirable. Peptides with DPP-IV inhibitory activity have been identified in a variety of food proteins. This review aims to provide an overview of food protein hydrolysates as a source of the DPP-IV inhibitory peptides with particular focus on milk proteins. In addition, the proposed modes of inhibition and structure–activity relationship of peptide inhibitors are discussed. Milk proteins and associated peptides also display insulinotropic activity and help regulate blood glucose in healthy and diabetic subjects. Therefore, milk protein derived peptide inhibitors may be a unique multifunctional peptide approach for the management of T2DM.

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Section: Gouda Cheeseunclassified

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory peptides for the management of type 2 diabetes

2013

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“…Incretins such as glucose dependent insulinotropic peptide (GIP) and more particularly glucagon-like peptide-1 (GLP-1) can enhance insulin secretion from pancreatic beta cells in the presence of glucose in vivo [2,42]. However, GLP-1 and GIP can be degraded by DDP-IV, resulting in major losses in the bioactive properties of these incretins.…”

Section: Introductionmentioning

confidence: 99%

“…Milk proteins, particularly, milk protein-derived peptides and amino acids have also been linked with the regulation of postprandial glycaemia and insulin secretion in normoglycaemic and type 2 diabetic subjects [6,8,23,24,26,32]. Peptides derived from -lactoglobulin have been shown to possess DDP-IV inhibitory activity in vitro [42,43].…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl peptidase IV inhibitory and antioxidative properties of milk protein-derived dipeptides and hydrolysates

2013

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Selected synthetic dipeptides and milk protein hydrolysates were evaluated for their dipeptidyl peptidase IV (DPP-IV) inhibitory properties, and their superoxide (SO) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. DPP-IV inhibition was seen with eight out of the twelve dipeptides and 5 of the twelve hydrolysates studied. Trp-Val inhibited DPP-IV, however, inhibition was not observed with the reverse peptide Val-Trp. The most potent hydrolysate inhibitors were generated from casein (CasH2) and lactoferrin (LFH1). Two Trp containing dipeptides, Trp-Val and Val-Trp, and three lactoferrin hydrolysates scavenged DPPH. The dipeptides had higher SO EC 50 values compared to the milk protein hydrolysates (arising from three lactoferrin and one whey protein hydrolysates). Higher molecular mass fractions of the milk protein hydrolysates were associated with the SO scavenging activity. Trp-Val and one lactoferrin hydrolysate (LFH1) were multifunctional displaying both DPP-IV inhibitory and antioxidant (SO and DPPH scavenging) activities. These compounds may have potential as dietary ingredients in the management of type 2 diabetes by virtue of their ability to scavenge reactive oxygen species and to extend the half-life of incretin molecules.

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“…Individual milk protein hydrolysates generated with -lactoglobulin (-Lg) 14,[16][17][18] α-lactalbumin (α-La) 18 , bovine serum albumin (BSA) 18 and lactoferrin (LF) 11,18 have also been identified as potent DPP-IV inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of dipeptidyl peptidase IV (DPP-IV) by tryptophan containing dipeptides

Nongonierma

Fitzgerald

2013

Food Funct.

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Twenty seven Trp containing dipeptides were evaluated for their ability to inhibit dipeptidyl peptidase IV (DPP-IV), a key enzyme involved in incretin hormone processing. Novel DPP-IV inhibitors were identified comprising of three potent dipeptides (Trp-Arg, Trp-Lys and Trp-Leu) with half maximum inhibitory concentration (IC 50 values) <45 mM. With the exception of Leu-Trp which was $20 times less potent than Trp-Leu, their reverse peptide did not inhibit DPP-IV. Trp-Asp was the only peptide studied herein with an N terminal Trp residue which was not a DPP-IV inhibitor. Phosphorylation resulted in an increase in DPP-IV IC 50 , giving values of 482.1 AE 12.9 and >11 000 mM for Trp-Thr and Trp-pThr, respectively. The mode of inhibition of these peptides was studied using Lineweaver and Burk kinetic analysis, which showed both competitive and non-competitive modes of inhibition depending on the peptide sequence. This suggested binding of the peptide inhibitors to different locations on DPP-IV. In silico analysis of the milk proteome revealed that some of the DPP-IV inhibitors identified herein may be released from milk proteins following enzymatic digestion. The results are relevant to understanding the mechanism(s) involved in DPP-IV inhibition by short peptides. This in turn may dictate a more targeted approach for the release of potent peptides from milk proteins with the view of developing biofunctional hydrolysates for the management of type 2 diabetes.

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Whey proteins as source of dipeptidyl dipeptidase IV (dipeptidyl peptidase-4) inhibitors

Cited by 177 publications

References 18 publications

Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory peptides for the management of type 2 diabetes

Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory peptides for the management of type 2 diabetes

Dipeptidyl peptidase IV inhibitory and antioxidative properties of milk protein-derived dipeptides and hydrolysates

Inhibition of dipeptidyl peptidase IV (DPP-IV) by tryptophan containing dipeptides

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