The development of bioactive peptides from dietary proteins as a dipeptidyl peptidase IV inhibitor for the management of type 2 diabetes

Abstract

One of the new approaches to the management of type 2 diabetes mellitus (T2DM) consists of orally administered dipeptidyl peptidase-IV (DPP-IV) inhibitors. These synthetic drug inhibitors are reported to have some side effects and that subsequently limits their applications. There is a growing interest to develop natural DPP-IV inhibitors that will be potent without undesirable side effects. Many in vitro and some in vivo studies have highlighted the potential of food-derived peptides functioning as effective DPPIV inhibitors. Bioactive peptides within original food-derived proteins are inactive but can be activated by being released during food processing (by enzymatic hydrolysis or fermentation) or during gastrointestinal digestion. Hence, the utilization of computer-aided techniques as screening tools may be helpful in predicting the potential of food proteins as precursors of DPP-IV inhibitory peptides. This paper reviews the current literature on DPP-IV inhibitory peptides, focusing on their in vitro activity and in vivo antidiabetic effects. In addition, the feasibility of various in silico approaches is also summarized in this review.

Structural properties of bioactive peptides with α‐glucosidase inhibitory activity

“…[7] This has compelled the scientific community to search for novel α-glucosidase inhibitors especially from natural (and easily biorenewable) sources with lower side-effects such as plantbased phenolics [8,9] and bioactive peptides. This information can be used to design peptides with increased bioactivity [12] that can be developed as novel therapeutic agents. [11] In the last decade, many peptides with different biological activities have been described and are currently receiving great scientific attention whilst new ones are being continuously discovered.…”

The excision of N terminal two amino acids of a novel human parathyroid hormone analog with dipeptidylpeptidase

“…The N-terminus X-Ala-of Glucagon-like peptide-1 (GLP-1) was able to be degraded by DPPIV. The half life of GLP-1 was less than 2 min in vivo [7,[9][10][11]. Accordingly, as a hypothesis, hPTH', as a potential substrate of DPPIV could also be excised in vivo to present as its active form.…”

“…As a serine protease, it has a specificity to remove dipeptides from the N-terminus of substrate poly-peptides by cleaving postproline or alanine residues [6][7]. The catalytic reaction has relatively strict specificity to substrate.…”

“…This multifunctional enzyme is implicated in several biological processes, including the degradation of chemokines, neuropeptides, and incretin hormones, e.g. glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) [7]. Accordingly, as the substrate of DPPIV, hPTH' should be excised into [Arg11]hPTH(1-34)-Pro-Pro-Asp rapidly and combined with receptors after administration.…”

Protein Digestion-Derived Peptides and the Peripheral Regulation of Food Intake

“…Dipeptidyl peptidase IV is a serine exopeptidase that removes dipeptides from the N-terminal side of substrates, including GLP-1 and GIP, by cleaving post-proline or -alanine residues (81). It cleaves and de facto quickly inactivates GLP-1 following its secretion and therefore appears as a strong inhibitor of its activities (82).…”