Characteristics of Food Protein-Derived Antidiabetic Bioactive Peptides: A Literature Update

Abstract

Diabetes, a glucose metabolic disorder, is considered one of the biggest challenges associated with a complex complication of health crises in the modern lifestyle. Inhibition or reduction of the dipeptidyl peptidase IV (DPP-IV), alpha-glucosidase, and protein-tyrosine phosphatase 1B (PTP-1B) enzyme activities or expressions are notably considered as the promising therapeutic strategies for the management of type 2 diabetes (T2D). Various food protein-derived antidiabetic bioactive peptides have been isolated and verified. This review provides an overview of the DPP-IV, PTP-1B, and α-glucosidase inhibitors, and updates on the methods for the discovery of DPP-IV inhibitory peptides released from food-protein hydrolysate. The finding of novel bioactive peptides involves studies about the strategy of separation fractionation, the identification of peptide sequences, and the evaluation of peptide characteristics in vitro, in silico, in situ, and in vivo. The potential of bioactive peptides suggests useful applications in the prevention and management of diabetes. Furthermore, evidence of clinical studies is necessary for the validation of these peptides' efficiencies before commercial applications.

Keywords: DPP-IV inhibitors; PTP-1B inhibitors; bioactive peptides; bioassay-guided methods; type 2 anti-diabetes; α-glucosidase inhibitors.

Figure 1

Schematic representation of the mechanism for the glucose-lowering action of DPP-IV inhibitors. GLP-1 and GIP are substrates for the DPP-IV enzyme that hydrolyzes them into shorter and inactive molecules. Note: DPP-IV, dipeptidyl peptidase IV; GIP, glucose-dependent insulinotropic polypeptide; and GLP-1, glucagon-like peptide-1.

Figure 2

Mechanism of action of alpha-glucosidase inhibitors.

Figure 3

Workflow for discovering DPP-IV inhibitory peptides from food-derived proteins.

Figure 4

Food protein-derived hydrolysates displaying in vitro dipeptidyl peptidase (DPP-IV) half maximal inhibitory concentration (IC₅₀) values (2016–2020).

Figure 5

Frequency analysis of amino acid residues contained in highly DPP-IV inhibition peptides (IC₅₀ < 100 µM) using WebLogo.

Figure 6

Inhibition modes of DPP-IV inhibitory peptides. (A) The complexion of the natural substrate (GLP-1) of DPP-IV and DPP-IV enzyme. DPP-IV inhibitors prevent DPP-IV enzymes from cleavage substrates through binding to active sites of DPP_IV as (B) competitive inhibition presenting via the Lineweaver-Burk plot results with a stable Vmax value and decreasing Km value based on the inhibitor concentrations; interaction at the secondary binding sites of DPP-IV as (C) non-competitive inhibition that performs a constant Km value and reducing Vmax value; and (D) uncompetitive inhibition that shows increasing Km value and decreasing Vmax value depending on the levels of inhibitors.