In Vivo and In Vitro Comparison of the DPP-IV Inhibitory Potential of Food Proteins from Different Origins after Gastrointestinal Digestion

Abstract

Dipeptidyl-peptidase IV (DPP-IV) plays an essential role in glucose metabolism by inactivating incretins. In this context, food-protein-derived DPP-IV inhibitors are promising glycemic regulators which may act by preventing the onset of type 2 diabetes in personalized nutrition. In this study, the DPP-IV-inhibitory potential of seven proteins from diverse origins was compared for the first time in vitro and in vivo in rat plasma after the intestinal barrier (IB) passage of the indigested proteins. The DPP-IV-inhibitory potentials of bovine hemoglobin, caseins, chicken ovalbumin, fish gelatin, and pea proteins were determined in rat plasma thirty minutes after oral administration. In parallel, these proteins, together with bovine whey and gluten proteins, were digested using the harmonized INFOGEST protocol adapted for proteins. The DPP-IV half-maximal inhibitory concentration (IC50) was determined in situ using Caco-2 cells. The DPP-IV-inhibitory activity was also measured after IB passage using a Caco2/HT29-MTX mixed-cell model. The peptide profiles were analyzed using reversed-phase high-performance liquid chromatography tandem mass spectrometry (RP-HPLC-MS/MS) with MS data bioinformatics management, and the IC50 of the identified peptides was predicted in silico. The in vitro and in vivo DPP-IV-inhibitory activity of the proteins differed according to their origin. Vegetable proteins and hemoglobin yielded the highest DPP-IV-inhibitory activity in vivo. However, no correlation was found between the in vivo and in vitro results. This may be partially explained by the differences between the peptidome analysis and the in silico predictions, as well as the study complexity.

In vitro comparison of whey protein isolate and hydrolysate for their effect on glucose homeostasis markers

“…dWPH decreases TEER and increases apparent permeability after 2 hours of incubation at a concentration of 31.25 mg.mL -1 but has no effect at 10 mg.mL -1 (Figure 3B and 3C). This is in agreement with our already published result which showed that a digested whey protein isolate decreased the TEER of Caco-2/HT-29MTX monolayer (29). The apparent permeability coefficient calculated with 31.25 mg.mL -1 of dWPH remained however acceptable (9,2.10 -7 ± 6,2.10 -7 cm.s -1 ).…”

“…Recently, we showed that the origin of the proteins led to different gastrointestinal-resistant peptidomes notably as a result of their native sequence, their digestibility and their conformation. These differences impacted the inhibitory potential of the DPP-IV activity, in vitro and in situ at the intestinal level but also in vivo in rat plasma (29). In contrast, in the present study, pre-hydrolysis of whey proteins did not modify the DPP-IV activity inhibitory effect in vitro and in situ at the intestinal level before the passage of the intestinal barrier.…”

“…The model described by Fleury et al with minor adaptations was used for the analysis of the IB passage (29), a recognized IB model using cocultured intestinal epithelial absorptive (Caco-2) and goblet (HT29-MTX) differentiated cells (30,31). In brief, Caco-2 and HT29-MTX cells were seeded at a ratio of 90/10 and a density of 20,000 cells per cm² on inserts (microporous PET membrane, 3 μm pore size, Corning, Glendale, CA, USA) and grown for 21 days to ensure good cell differentiation.…”

<em>In Vitro </em>and <em>in vivo</em> Experimental Approaches for Antidiabetic Activity Assessment: A Methodological Review

“…• It's not causing the weight gain or hypoglycemia [53] • Maybe have drug interaction risk [53] PTP-1B inhibition…”

Bioactive Peptides in Human Health and Disease

“…Dietary proteins can be an excellent source of bioactive peptides, with several biological activities. Fleury et al [ 7 ] investigated the ability of some dietary proteins and the peptides derived from their in vitro digestion to inhibit the activity of the enzyme dipeptidyl-peptidase IV (DPP-IV). This enzyme is a pharmacological target in type-2 diabetes therapy since it is involved in the degradation of the insulinotropic incretin hormones.…”