Discovery of Food-Derived Dipeptidyl Peptidase IV Inhibitory Peptides: A Review

Abstract

Diabetes is a chronic metabolic disorder which leads to high blood sugar levels over a prolonged period. Type 2 diabetes mellitus (T2DM) is the most common form of diabetes and results from the body's ineffective use of insulin. Over ten dipeptidyl peptidase IV (DPP-IV) inhibitory drugs have been developed and marketed around the world in the past decade. However, owing to the reported adverse effects of the synthetic DPP-IV inhibitors, attempts have been made to find DPP-IV inhibitors from natural sources. Food-derived components, such as protein hydrolysates (peptides), have been suggested as potential DPP-IV inhibitors which can help manage blood glucose levels. This review focuses on the methods of discovery of food-derived DPP-IV inhibitory peptides, including fractionation and purification approaches, in silico analysis methods, in vivo studies, and the bioavailability of these food-derived peptides. Moreover, food-derived DPP-IV inhibitory peptides discovered during this decade are listed and distributed in a 3D scatter plot graph based on their IC₅₀, molecular weight, and grand average of hydropathicity values, which can help us to understand the relationship between the features of the peptides and their activities.

Keywords: dipeptidyl-peptidase IV inhibition; food proteins; peptides; type 2 diabetes mellitus.

Figure 1

Workflow of active peptides discovery. Those “Active Fractions” in purple color were further used for active peptides purification and identification.

Figure 2

Distribution of known DPP-IV inhibitory peptides. Red dot: tripeptide IPI. Blue square: dipeptide Gly-Pro (GP). (A) 3D distribution of 222 peptides based on their IC₅₀, MW, and GRAVY values; (B) distribution of 222 peptides according to IC₅₀ and MW; (C) distribution of peptides according to IC₅₀ and GRAVY values; (D) distribution of peptides according to MW and GRAVY values; and (E) and (F) MW and GRAVY value distributions of the 222 peptides, respectively, based on the total number of peptides.