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.

Objectives There are limited data available on true ileal nitrogen and amino acid digestibility of protein sources. The goal of this study was thus to determine for the first time in healthy volunteers the ileal digestibility of zein and whey proteins. Methods Twenty-two volunteers (10 women and 12 men; aged 37 ± 12y) were equipped with a double lumen intestinal tube positioned at the ileal level. They received a single meal of protein-free biscuits and a drink containing zein (n = 8), whey protein isolate (WPI, n = 7) or no protein (protein-free, n = 7). 13C-inuline was added to the drink as a non-absorbable marker. Ileal effluents were collected over a 9-h period after meal ingestion. Total nitrogen content was measured in effluents and correction for endogenous losses evaluated with the protein-free group was used to determine true digestibility of zein and WPI proteins. Results The mean ileal endogenous nitrogen flow was 3.89 ± 1.41mmol/h (mean ± SD). For zein, mean dietary nitrogen flow rate was 12.1 ± 6.9mmol/h, reaching 23.6 ± 13.5mmol/h 4h after the meal. In comparison, mean dietary nitrogen flow rate for WPI was significantly lower (1.6 ± 1.2mmol/h, P < 0.0001). Ileal apparent and true nitrogen digestibility of zein was markedly lower than WPI (11.7 ± 11.4% and 63.9 ± 5.9% for apparent digestibility of zein and WPI respectively, P < 0.0001; 32.2 ± 11.0% and 89.0 ± 5.8% for true digestibility of zein and WPI respectively, P < 0.0001). Conclusions In conclusion, we showed that zein is a poorly digestible protein. Among all the dietary proteins evaluated in humans, it presents the lowest value. Such a poor digestibility might be explained by the very low solubility of zein. On the contrary, the ileal digestibility of WPI is relatively high but lower than total milk proteins or casein measured in humans (around 95%). To further examine the digestibility of these 2 protein sources, amino acids bioavailability will be next evaluated. Funding Sources This study is funded by the Global Dairy Platform Incorporated. Supporting Tables, Images and/or Graphs

Several studies have demonstrated that high protein diets improve glucose homeostasis. Nevertheless, the mechanisms underlying this effect remain elusive. This exploratory study aims to screen and compare the acute effects of dietary proteins from different sources on intestinal glucose absorption. Six dietary proteins from various sources were thus selected and digested thanks to the INFOGEST static gastrointestinal digestion protocol. The digested proteins were able to decrease intestinal glucose absorption in vitro and ex vivo. Moreover, acute ingestion of casein and fish gelatin led to improved glucose tolerance in Wistar rats without significant effect on insulin secretion. In parallel, GLUT2 mRNA expression in enterocytes was decreased following short-term incubation with some of the digested proteins. These results strengthen the evidence that digested protein-derived peptides and amino acids are key regulators of glucose homeostasis and highlight their role in intestinal glucose absorption.