Food-derived dipeptidyl-peptidase IV inhibitors as a potential approach for glycemic regulation – Current knowledge and future research considerations

Abstract

Background: Diabetes, which currently affects 1 in 11 adults, is considered one of the biggest worldwide health crises of the 21 st century. Over the last decade, synthetic inhibitors of the enzyme dipeptidyl-peptidase IV (DPP-IV) have emerged as an effective pharmaceutical approach for the management of type 2 diabetes. These molecules exert their beneficial effect by preventing the inactivation of gut-derived hormones that play a pivotal role in glycemic regulation. More recently, food components have been suggested as sources of DPP-IV inhibitors with the potential to help manage blood glucose levels.Scope and approach: This review examines the sources, production, molecular characteristics and modes of action of food-derived DPP-IV inhibitors. Insights into the needs for future research to validate their efficacy and to establish their application in the management of type 2 diabetes are also discussed. Key findings and conclusions:To date, hydrolysates of protein from a variety of food commodities, including both plant and animal sources, have been shown to be able to inhibit the activity of the DPP-IV enzyme. Moreover, a number of peptides, either isolated from these hydrolysates or synthetically produced, as well as non-protein-derived compounds such as polyphenols, have also been identified as DPP-IV inhibitors. These food-derived constituents present different degrees of potency and modes of action on the DPP-IV enzyme. While their effectiveness in humans is currently unknown, findings from in vitro and animal studies conducted to date warrant further research to evaluate their potential as functional food ingredients for glycemic regulation.

A Comprehensive Review of Corn Protein‐derived Bioactive Peptides: Production, Characterization, Bioactivities, and Transport Pathways

“…Currently, extensive efforts have been put toward the development of food‐derived peptides enabling to inhibit the activity of DPP‐IV, which may lead to type 2 diabetes for its antagonism ability against the incretin hormones glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) (Lacroix & Li‐Chan, ; Nongonierma & FitzGerald, ). DPP‐IV inhibitory peptide has been developed as a potential approach in the therapy of type 2 diabetes, and a considerable amount of studies have revealed that plentiful food protein‐derived peptides shown potent DPP‐IV inhibitory activity, including plant‐derived peptides such as casein, rice, and soy as well as animal‐derived peptides such as milk and pork (Huang, Hung, Jao, Tung, & Hsu, ; Nongonierma & FitzGerald, , ).…”

Learnings from quantitative structure–activity relationship (QSAR) studies with respect to food protein-derived bioactive peptides: a review

“…Two of the peptides (Ala-Trp and Val-Trp) were inactive towards renin, while the renin inhibitory activity determined experimentally was lower or of the same order as the predicted inhibition for Leu-Trp and Ile-Trp, respectively. 53 In addition, Ile-Trp (IC 50 ¼ 2.3 AE 0.07 mM) was a newly identied renin inhibitory peptide also displaying high ACE inhibitory activity (IC 50 ¼ 4.74 AE 0.04 mM). Interestingly, Ile-Trp had previously been shown to induce a signicant reduction in SBP in SHR studies.…”

Bioinformatics of edible yellow mealworm (Tenebrio molitor) proteome reveal the cuticular proteins as promising precursors of dipeptidyl peptidase‐IV inhibitors

“…Inhibiting DPP-IV activity leads to an increase of insulin secretion and therefore a decrease in blood glucose level in vivo (Mochida, Hira, & Hara, 2010;Ishikawa et al, 2015). DPP-IV (also known as DPP-4 or cluster of differentiation 26) is a soluble or membrane-anchored enzyme that degrades incretin hormones, glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide, inactivating more than 95% of the GLP-1 produced in the body (Lacroix & Li-Chan, 2016). DPP-IV (also known as DPP-4 or cluster of differentiation 26) is a soluble or membrane-anchored enzyme that degrades incretin hormones, glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide, inactivating more than 95% of the GLP-1 produced in the body (Lacroix & Li-Chan, 2016).…”

“…Food-derived peptides have low biostability due to their scissile peptide bonds (Udenigwe & Fogliano, 2017), and their bioavailability is reported to be in amounts as low as pico-and nanomolar concentrations (Xu, Hong, Wu, & Yan, 2019). Moreover, inhibitory effect of food peptides is lower than that of rationally designed synthetic gliptins (Lacroix & Li-Chan, 2016). Nonetheless, food protein-derived peptides are promising as functional ingredients for managing T2D and as natural adjuvant to support the effect and reduce the use of synthetic DPP-IV inhibiting drugs.…”