The therapeutic actions of DPP-IV inhibition are not mediated by glucagon-like peptide-1

Nauck, Michael A.; El-Ouaghlidi, A.

doi:10.1007/s00125-005-1704-8

Cited by 81 publications

(47 citation statements)

References 24 publications

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“…However, contradictory results are also reported in the literature with some studies indicating no direct correlation between the insulinotropic properties of DDP-IV inhibitors and plasma GLP-1 levels. This suggests that other incretins and neuropeptides also play a role in the regulation of blood glucose homeostasis in the presence of DDP-IV inhibitors [27].…”

Section: Introductionmentioning

confidence: 99%

“…DDP-IV is located at the surface of various cells and can also be found in a soluble form in the circulation [2]. An increase in circulating GLP-1 by a factor 4 to 6 has been reported in vivo following the utilization of DDP-IV drug inhibitors [27]. DDP-IV inhibitors are reported to protect GLP-1 and GIP from enzymatic degradation and therefore can increase their half-life, resulting in a prolonged action in vivo [2].…”

Section: Introductionmentioning

confidence: 99%

“…DDP-IV inhibitors are reported to protect GLP-1 and GIP from enzymatic degradation and therefore can increase their half-life, resulting in a prolonged action in vivo [2]. Peptide-like DDP-IV inhibitors such as vildagliptin and saxagliptin [17] have been shown to normalize blood glucose concentration in type 2 diabetic subjects [27]. However, contradictory results are also reported in the literature with some studies indicating no direct correlation between the insulinotropic properties of DDP-IV inhibitors and plasma GLP-1 levels.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2013

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“…DPP-IV inhibitory drugs are utilized to prevent incretin degradation in vivo, thereby increasing their half-life. 2,3 Binding of various competitive DPP-IV inhibitors has been described at the active site of DPP-IV, mainly through interactions with an hydrophobic pocket, composed of Tyr-666, 40 Tyr-662, Val-711, Val-656 and Trp-659. 4 However, a secondary binding site for DPP-IV inhibitors has been described for N terminus of the human immunodeficiency virus-1 (HIV) transactivator Tat.…”

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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“…Nauck and El-Ouaghlidi present five arguments suggesting that GLP-1 is not the only-or at least not the major-mediator of the glucose-lowering actions of DPP-IV [26]. Holst and Deacon acknowledge these arguments, but maintain that current evidence nonetheless supports a dominant role for GLP-1 [27].…”

mentioning

confidence: 99%

What mediates the benefits associated with dipeptidyl peptidase-IV inhibition?

Åhrén

2005

Diabetologia

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The therapeutic actions of DPP-IV inhibition are not mediated by glucagon-like peptide-1

Cited by 81 publications

References 24 publications

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

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

What mediates the benefits associated with dipeptidyl peptidase-IV inhibition?

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