Milk Peptides Research Articles

The optimization of peptides - producing conditions for antioxidant peptides in goat milk by Lactobacillus casei L61.

The chemical synthesis of antioxidants has exposed more and more of their disadvantages. Therefore, the development of safe, healthy and efficient natural antioxidants has become a research hotspot. At present, antioxidant peptides are gradually becoming more popular due to their strong antioxidant activity and high safety. The aim of this experiment was to obtain the optimum fermentation conditions for producing antioxidant peptides from Lactobacillus casei L61. The effects of various factors (fermentation temperature, fermentation time, concentration of regenerated milk and inoculum) on the production of antioxidant peptides by Lactobacillus casei L61 were studied using a single factor test. Four methods (DPPH radical scavenging activity, the ability to chelate iron, hydroxyl radical scavenging rate, total reduction force) were used to determine antioxidant activity in vitro. The optimum fermentation conditions were determined by orthogonal experiment. The results showed that the optimal fermentation conditions for the production of antioxidant peptides by L61 were 11% reconstituted milk, 5% inoculated milk, fermentation at 41℃ and 16 hours of fermentation time. Under these conditions, the results of the orthogonal test showed that the DPPH radical scavenging rate of the whey sample was 59.97 ±0.87%, which was higher than those of the other 9 groups, and significantly higher than that of the control group (41.97 ±1.37%). The concentration of reconstituted milk and the amount of inoculated milk had a significant effect on the production of antioxidant peptides by Lactobacillus casei L61. It provides a reference for the optimization of the fermentation nutritional composition of antioxidant peptides produced by Lactobacillus casei L61.

The optimization of peptides – producing conditions for antioxidant peptides in goat milk by Lactobacillus casei L61 [pdf

The optimization of peptides – producing conditions for antioxidant peptides in goat milk by Lactobacillus casei L61 [pdf

Insight into the bovine milk peptide LPcin-YK3 selection in the proteolytic system of Lactobacillus species.

Antimicrobial peptides are class of small, positively charged peptides known for their broad‐spectrum antimicrobial activity. Antimicrobial activities for most antimicrobial peptides have largely remained elusive, particularly in the lactic acid bacteria. However, recently our investigation using LPcin‐YK3, an antimicrobial peptide from bovine milk, suggests that in vitro antimicrobial activity was reduced over 100‐fold compared with pathogenic bacteria. Additionally, for the structural study of how antimicrobial peptide undergoes its reaction at the proteolytic pathway of lactic acid bacteria based on degradation assay and propidium iodide staining, we performed molecular docking for interaction between oligopeptide‐binding protein A and LPcin‐YK3 peptide. Given that degradation related to the LPcin‐YK3 peptide in lactic acid bacteria proteolytic system, the inhibitory inactivity of LPcin‐YK3 against beneficial lactic acid bacteria strains may be one of the primary pharmacological properties of recombinant peptide discovered in bovine milk. These results provide structural and functional insights into the proteolytic mechanism and possibility as a putative substrate of oligopeptide‐binding protein A in respect of LPcin‐YK3 peptide.

Recombinant Lactaptin Induces Immunogenic Cell Death and Creates an Antitumor Vaccination Effect in Vivo with Enhancement by an IDO Inhibitor.

Natural compounds of various origins are intensively investigated for their antitumor activity. Potential benefits of antitumor therapy can be achieved when cytotoxic agents kill cancer cells and these dying cancer cells drive adoptive immunity to the tumor. This strategy was successfully demonstrated for chemotherapeutic drugs that induce immunogenic type of cell death (ICD) with release of DAMPs (danger associated molecular patterns) and exposure of “eat me” signals. In this study, we demonstrated that recombinant human milk peptide lactaptin (RL2) induces death of cancer cells with ICD hallmarks in vitro with the release of ATP and high-mobility group box 1 protein (HMGB1) and exposure of calreticulin and HSP70 on the external cell membrane. RL2-treated cancer cells were efficiently engulfed by phagocytic cells. Using the syngeneic mouse model, we demonstrated that RL2-treated MX-7 rhabdomyosarcoma cells confer long-term immune-mediated protection against challenge with live MX-7 cells. We also analyzed the combinatorial antitumor effect of vaccination with RL2-treated cells and the inhibition of indoleamine 2,3-dioxygenase (IDO) with ethyl pyruvate. Compared to solo anti-tumor immunization with RL2-treated cells, additional chemical inhibition of IDO demonstrated better long-term antitumor responses than vaccination alone.

Production of an antihypertensive peptide from milk by the brown rot fungus Neolentinus lepideus

Fermented milk has been shown to have beneficial effects on human health exerted through its bioactive peptides. The lactose-fermenting brown rot fungus Neolentinus lepideus has been shown to ferment milk; however, its ability to produce bioactive peptides has not been explored. This study, therefore, aimed to investigate the ability N. lepideus for the production of antihypertensive peptides in fermented milk and to characterize the peptides. Here we have used 9% skim milk as the substrate and fermented it with the mycelia of N. lepideus. The fermented milk exhibited higher angiotensin I-converting enzyme (ACE) inhibitory activity as compared to the commercially available sour milk containing Ile-Pro-Pro and Val-Pro-Pro. As a result of isolation and purification by reverse-phase high-performance liquid chromatography, followed by peptide sequencing and MS analysis, the dipeptide Tyr-Pro (YP) was identified as an active peptide. The concentration of YP in the fermented milk reached up to 450 μg/ml, which was > twofold higher than the IC50 for ACE inhibition. Subsequently, the antihypertensive effect of YP was validated through intravenous injection of the peptide, which exhibited a significant lowering of blood pressure in a rat model of genetic hypertension. In addition, the transcriptomic analysis revealed the probable role of the carboxypeptidases for the increased yield of YP. These results together indicated that the fermentation with basidiomycete fungus could be a viable approach to produce bioactive peptides, and may, therefore, be applicable in the development of a cost-effective mass production system for functional peptides.

Characterization of casein-derived peptide bioactivity: Differential effects on angiotensin-converting enzyme inhibition and cytokine and nitric oxide production

Lactic acid bacteria (LAB) are used as starter cultures in the production of fermented dairy products and have the potential to confer bioactivity relevant to cardiovascular health, as they possess extensive proteolytic systems that liberate small bioactive peptides from larger milk proteins. Certain casein-derived peptides released by various LAB strains during fermentation have been shown to reduce hypertension and to modulate the immune system. We investigated the growth and peptide production of 2 LAB strains, Lactobacillus helveticus R0389 and Lactocaseibacillus rhamnosus R0011, their immunomodulatory activities, as well as their abilities to inhibit the angiotensin-converting enzyme (ACE). Peptide fractions collected from the cell-free supernatant of both medium-grown and milk fermentation cultures were assessed for ACE-inhibitory activity and their effects on the production of proinflammatory and regulatory cytokines by human THP-1 monocytes. Cultures were grown in medium, with or without supplementation with 0.1% casein, or in 3.25% milk fermented with each LAB strain. Casein supplementation increased the growth rate of both LAB strains, and significantly increased ACE-inhibitory activity of peptide fractions collected from both L. helveticus R0389 and L. rhamnosus R0011 cultures grown for 12 h. Fermentation peptide fractions of L. rhamnosus R0011 showed comparable ACE-inhibitory activity to known ACE inhibiting peptides Val-Pro-Pro and Ile-Pro-Pro (up to 79% inhibition) with a significant difference between culture peptide fractions and acidified and nonacidified control fractions collected after 6 d of fermentation. Many milk and casein-derived peptides reported in previous studies have been identified as part of a larger bioactive fraction. We synthesized a group of these peptides to individually assess both ACE-inhibitory and immunomodulatory activity. The known ACE inhibitors Val-Pro-Pro and Ile-Pro-Pro showed similar ACE inhibition to previously published results, while also inducing the production of the regulatory cytokine IL-10 by monocytes in the presence and absence of a proinflammatory stimulant. These synthesized peptides could also induce the production of nitric oxide (NO), a potent vasodilator, in human endothelial cell cultures. Investigating the relationships among these bioactive properties could improve the use of probiotic organisms and their secreted products in the food industry.

Bioactive peptides derived from human milk proteins: an update.

Human milk contains a variety of bioactive proteins, and some of the bioactivities are exerted only after proteins are digested in the gastrointestinal tract. This review aims to overview recent studies on bioactive peptides in human milk and gastric digesta of breast-fed infants. Milk protein-derived peptides are endogenously present in human milk, and some of them have been reported to be bioactive peptides, such as a homologue of caseinophosphopeptide, an antimicrobial peptide, and an immunomodulatory peptide. A larger number of peptides are identified in gastric aspirates from breast-fed infants, and bioactive peptides such as angiotensin I-converting enzyme-inhibitory peptides, an antioxidative peptide, opioid agonist peptides are only found in the digesta of human milk but not in human milk per se. Casein is the greatest source of released bioactive peptides. Technological advances have considerably increased our capability to identify and characterize peptides derived from human milk proteins. However, their physiological significance and the roles of these bioactive peptides in growth and development of breast-fed infants have not yet been sufficiently elucidated, and further in-vivo experiments and clinical trials are warranted.

Correction: Sartorius et al. "Postprandial Effects of a Proprietary Milk Protein Hydrolysate Containing Bioactive Peptides in Prediabetic Subjects" Nutrients 2019, 11, 1700.

Milk proteins have been hypothesized to protect against type 2 diabetes (T2DM) by beneficially modulating glycemic response, predominantly in the postprandial status. This potential is, amongst others, attributed to the high content of whey proteins, which are commonly a product of cheese production. However, native whey has received substantial attention due to its higher leucine content, and its postprandial glycemic effect has not been assessed thus far in prediabetes. In the present study, the impact of a milk protein hydrolysate of native whey origin with alpha-glucosidase inhibiting properties was determined in prediabetics in a randomized, cross-over trial. Subjects received a single dose of placebo or low- or high-dosed milk protein hydrolysate prior to a challenge meal high in carbohydrates. Concentration–time curves of glucose and insulin were assessed. Incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by low-dosed milk peptides compared to placebo (p = 0.0472), and a minor insulinotropic effect was seen. A longer intervention period with the low-dosed product did not strengthen glucose response but significantly reduced HbA1c values (p = 0.0244). In conclusion, the current milk protein hydrolysate of native whey origin has the potential to modulate postprandial hyperglycemia and hence may contribute in reducing the future risk of developing T2DM.

Milk Peptides Survive In Vivo Gastrointestinal Digestion and Are Excreted in the Stool of Infants

Human milk peptides released by gastrointestinal proteases have been identified with bioactivities that can benefit the infant but must first reach their respective sites of activity. Peptides in the stool either survived to or were released inside the intestinal tract, and thus had the opportunity to exert bioactivity there. However, it is unknown whether any milk peptides, bioactive or not, can survive in the stool of infants. The aim of this study was primarily to identify milk peptides in infant stool samples and secondarily test the hypotheses that the milk peptide profiles of stools are different between preterm infants at different days of life and between preterm and term infants. Infant stool samples were collected from 16 preterm infants (<34 weeks gestational age) at 8 or 9 and 21 or 22 days of life (DOL), and from 10 term infants (>34 weeks gestational age) at 8 or 9 DOL. Milk peptides were isolated from the stool samples and identified using tandem MS. The peptide counts and abundances were compared between infant groups. In total, 118 exclusively milk-derived peptides from the caseins and α-lactalbumin were present in the stool samples, including some peptides with known or potential bioactivity. The remaining 8014 identified peptides could be derived either from milk or endogenous proteins. Although many individual milk peptides were significantly different between preterm infants at 8/9 and 21/22 DOL and between preterm and term infants, total peptide abundance and count were similar for all 3 groups. This is the first study to confirm the survival of milk peptides in the stool of infants. Some of the peptides had potential bioactivities that could influence infant gut development. These results are important to understand the physiological relevance of human milk peptides to the infant.

Identification and characterization of the gene encoding an extracellular protease from haloarchaeon Halococcus salifodinae

Extracellular proteases from haloarchaea (halolysins) can resist high salt conditions. In this study, the gene encoding a halolysin from Halococcus salifodinae was identified. The hlyA gene encoded an active halolysin with the classical Asp-His-Ser catalytic triad of serine proteases. Site-directed mutagenesis showed that the three cysteine residues in the catalytic domain were important for the extracellular proteolytic activity and displayed an additive effect on the activity. Truncation mutants of the C-terminal extension (CTE) domain displayed very low or almost no extracellular protease activity towards milk and small peptide substrates, indicating its importance for the function of HlyA. CTE can be functionally interchangeable among halolysins. Additionally, the HlyA expressing strain as a starter culture for fish sauce fermentation significantly increased the peptide release and total free amino acid content in fish sauce. This study enriches our knowledge of the key amino acid residues and domains of halolysins, and provides an opportunity for applications of halolysins in fish sauce fermentation.

Süt ve Süt Ürünlerinde Bulunan Biyoaktif Peptitler, Antimikrobiyal Özellikleri ve İnsan Sağlığı Üzerindeki Etkileri

Son yıllarda gıdaların besin değerinin yanı sıra fonksiyonel özellikleri de önem kazanmıştır. Biyoaktif peptitler, insan sağlığı üzerine olumlu etkilere sahip proteinlerin parçalanma ürünleri olarak tanımlanmıştır. İnek sütünde bulunan biyoaktif peptitler, süt proteinlerinin proteolitik enzimlerle hidrolizi sonucunda açığa çıkar. Biyoaktif peptitler, bağışıklık sistemini uyarıcı, mineral bağlayıcı, antimikrobiyal, antihipertansif, opioid, antioksidatif, antiülseratif, antitrombotik, antitümör ve apoptoz etki gibi değişik biyokimyasal ve fizyolojik özelliklere sahiptir. Bu çalışmada süt ve süt ürünlerinde bulunan biyoaktif peptitler, antimikrobiyal özellikleri ve insan sağlığı üzerindeki etkileri değerlendirilmiştir.

Dairy-derived peptides for satiety

Abstract Satiety hormones produced in the gastrointestinal tract are key players in influencing appetite and food intake. Dairy proteins that target these gastric signals have the potential to make one feel ‘fuller for longer’. While effects of whey and casein on appetite and food intake are well documented, this review focuses on individual dairy peptides. The evidence of these peptide bioactives on satiety signaling in vitro using cellular models and in vivo via intervention trials is summarized. Dairy protein hydrolysates are also reviewed for their satiating properties. How their efficacy compares to other notable food derived peptides and how this efficacy can be lost, bolstered or protected during gut transit is also summarized.

Angiotensin-I-converting enzyme inhibitory peptides in milk fermented by indigenous lactic acid bacteria.

Background and Aim:Fermented milk can be used to produce antihypertensive peptides. Lactic acid bacteria (LAB) with its proteolytic system hydrolyze milk protein during fermentation to produce several peptides, which include antihypertensive bioactive peptides. This study aimed to investigate the ability of indigenous LAB for the production of angiotensin-I-converting enzyme inhibitory (ACE-I) peptides in fermented milk and to characterize the ACEI peptides.Materials and Methods:Reconstituted milk (11%) inoculated with ten LAB isolates, and then incubated at 37°C until it reaches pH 4.6. The evaluation was carried out for LAB count, lactic acid concentration, peptide content, and ACE-I activity. The low molecular weight (MW) peptides (<3 kDa) were identified using Nano LC Ultimate 3000 series system Tandem Q Exactive Plus Orbitrap high-resolution mass spectrometry.Results:The result showed that the ten LAB isolates were able to produce ACE-I in fermented milk with the activities in the range of 22.78±2.55-57.36±5.40%. The activity of ACE-I above 50% produced by Lactobacillus delbrueckii BD7, Lactococcus lactis ssp. lactis BD17, and Lactobacillus kefiri YK4 and JK17, with the highest activity of ACE-I produced by L. kefiri YK4 (IC50 0.261 mg/mL) and L. kefiri JK17 (IC50 0.308 mg/mL). Results of peptide identification showed that L. kefiri YK 4 could release as many as 1329, while L. kefiri JK 17 could release 174 peptides. The peptides produced were 95% derived from casein. The other peptides were from ά-lactalbumin, β-lactoglobulin, and serum amyloid A. The peptides produced consisted of 6-19 amino acid residues, with MWs of 634-2079 Dalton and detected at 317-1093 m/z. A total of 30 peptides have been recognized based on literature searches as ACE-I peptides (sequence similarity: 100%).Conclusion:L. kefiri YK4 and JK17 are the potential to be used as starter cultures to produce the bioactive peptide as ACE-I in fermented milk.

Effects of oral administration of colostrum whey in peripartum goat on antimicrobial peptides in postpartum milk.

The present study was conducted to examine whether colostrum supplementation in peripartum goats increases the antimicrobial peptides in their milk. Goats were orally administered 2ml of colostrum whey products (colostrum group) or water (control group) daily, from 2weeks before until 2weeks after kidding. Body weights of mothers and kids were measured. Blood, milk, and fecal samples were collected from the mothers, and blood samples were collected from the kids. Concentrations of milk antimicrobial peptides (beta-defensin, cathelicidin, lactoferrin, S100A7, lactoperoxidase, and immunoglobulin A [IgA]) were determined. IgA and nutritional parameters (glucose, total cholesterol, triglyceride, ketone bodies, and non-esterified fatty acids) were also determined in the blood of mothers and kids. Milk IgA and lactoferrin concentrations were higher in the colostrum group than in the control group. Conversely, lower milk concentrations of S100A7 were observed in the colostrum group than that in the control group. Plasma IgA concentrations were higher for kids from the colostrum group than for those from the control group. These results suggest that oral administration of colostrum in pregnant goats increases IgA concentration in postpartum milk, which can subsequently improve the health of their kids.

Application of Plackett-Burman Design in Screening Casein and Prebiotics for the Production of ACE Inhibitory Peptides from Cow Milk Fermented by L. bulgaricus LB6

Abstract Prebiotics can play an important role in functional foods. In this paper, casein and five probiotics were selected to study the effects on ACE inhibitory peptides in fermented milk of L. bulgaricus LB6 through Plackett-Burman design, so as to improve the production of ACE inhibitory peptides. The results showed that xylooligosaccharides (XOS), fructosaccharide (FOS) and inulin had the most significant effect on the yield of ACE inhibitory peptides. Optimization added the amount of the three prebiotics added, that is, the amount of XOS added was 0.7%, the amount of FOS added was 1.1%, and the amount of inulin added was 0.7%. It provides a basis for subsequent optimization experiments.

Orally administered milk-derived tripeptide improved cognitive decline in mice fed a high-fat diet.

The functions of the brain, which is thought of as an organ highly independent from the periphery, are often affected by the peripheral environment. Indeed, epidemiologic studies demonstrated that diabetes was a risk factor for dementia. It was also reported that the intake of dairy products, such as milk, reduces the risk of developing dementia. We found that mice on a short-term high-fat diet (HFD) for 1 wk had reduced cognitive function. Thus, using this acute model, we investigated the effects of milk-derived peptide on cognitive decline induced by HFD. Tyr-Leu-Gly (YLG), a tripeptide derived from αS1-casein, a major bovine milk protein, is released by gastrointestinal proteases. We found that orally administered YLG improved cognitive decline induced by 1-wk HFD intake in the object recognition test. YLG also improved cognitive decline in the object location test. Thus, we found that YLG improved cognitive decline induced by HFD. Next, we examined the effects of YLG on the hippocampus, a brain area essential for cognitive function. HFD intake decreased the number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells, and this decrease was improved by YLG administration. HFD intake decreased nerve growth factor (NGF) and glial cell line-derived neurotrophic factor, whereas YLG increased NGF and ciliary neurotrophic factor, suggesting that these neurotropic factors play a role in hippocampal neurogenesis after YLG administration. In conclusion, we demonstrated that 1-wk HFD reduced cognitive function. Furthermore, we found that YLG, a milk-derived tripeptide, improved cognitive decline in mice on HFD. The HFD reduced neural stem cell proliferation, and YLG improved this reduction. YLG is the first reported milk peptide to improve cognitive decline induced by HFD intake.-Nagai, A., Mizushige, T., Matsumura, S., Inoue, K., Ohinata, K. Orally administered milk-derived tripeptide improved cognitive decline in mice fed a high-fat diet.

Protective factors in mature human milk: a look into the proteome and peptidome of adolescent mothers’ breast milk

The characterisation of proteome and peptidome of adolescent mothers' breast milk brings important information to both mother's and infant's health; however, it has not been investigated. Bioactive peptides derived from milk proteins have numerous functions. The bioactivity of breast milk peptides includes anti-inflammatory and antimicrobial activities and regulation of gastrointestinal function. We aimed to characterise the proteome and peptidome of mature breast milk of adolescent mothers and investigate whether it is affected by lactational period. We used a combination of electrophoretic and nano-scale LC-quadrupole time-of-flight MS/MS (nLC-Q-TOF-MS/MS) techniques and bioinformatics to explore the proteome of human skimmed milk expressed by lactating adolescents in two groups according to postpartum period (up to 3 and over 5 weeks postpartum). This is the first study that analysed the proteome of adolescent mothers' breast milk produced during two periods of lactation using 1D-electrophoresis combined with nLC-Q-TOF-MS/MS analysis. Our results showed that the protein composition of adolescent milk varies independently of lactation stage and showed high inter-individual variation. A total of 424 proteins were identified in skimmed milk, of which 137 proteins were common to both groups. Most of the peptides found in adolescents' breast milk were not derived from major proteins in milk. Association maps showed several interactions between groups of peptides that pointed to the relevance of breast milk peptides to neonatal defensive system.

New Functional Ingredients Based on Microencapsulation of Aqueous Anthocyanin-Rich Extracts Derived from Black Rice (Oryza sativa L.).

The aqueous anthocyanin-rich extract derived from black rice (Oryza sativa L.) was encapsulated by freeze drying using milk proteins and peptides as coating materials. The molecular modelling approach indicated that all major casein fractions and whey proteins were able to bind at least one anthocyanin molecule. The hydrophobic interactions and hydrogen bonding across the interfaces appeared to be mainly responsible for the stabilizations of the complexes formed between the coating material and bioactive compounds. Two dark purple colored powders, differentiated by the ratio of the encapsulation materials used, rich in phytochemicals were obtained, with an encapsulation efficiency of up to 99%. The powders were tested for antioxidant activity, cytocompatibility, and thermal stability. The morphological structure of the powders highlighted the presence of encapsulated anthocyanins. Both powders showed a remarkable antioxidant activity of about 46 mM Trolox/g D.W., and cytocompatibility on the L929 fibroblast culture. At certain concentrations, both powders stimulated cell proliferation. The powders showed a good thermal stability between 75 and 100 °C for 15 min. The powders were tested in a food model system and checked for stability of phytochemicals during storage. The added value of the powders was demonstrated throughout the antioxidant activity, which remained unchanged during storage.

In vitro-digested milk proteins: Evaluation of angiotensin-1-converting enzyme inhibitory and antioxidant activities, peptidomic profile, and mucin gene expression in HT29-MTX cells

Over the past decades, several studies investigated the health-promoting functions of milk peptides. However, to date many hurdles still exist regarding the widespread use of milk-derived bioactive peptides, as they may be degraded during gastrointestinal digestion. Thus, the aim of our study was to in vitro digest intact whey protein isolate (WPI) and casein proteins (CNP), mimicking in vivo digestion, to investigate their bioactive effects and to identify the potential peptides involved. Whey protein isolate and CNP were digested using a pepsin-pancreatin protocol and ultra-filtered (3-kDa cutoff membrane). A permeate (<3 kDa) and a retentate (>3 kDa) were obtained. Soy protein was included as a control (CTR). Angiotensin-1-converting enzyme inhibitory (ACE1-I) and antioxidant activity (AOX) were assessed and compared with those observed in undigested proteins and CTR. Furthermore, the permeate was characterized by nano-liquid chromatography electrospray ionization tandem mass spectrometry (LC-nano ESI MS/MS) using a shotgun peptidomic approach, and retentate was further digested with trypsin and analyzed by MS using a shotgun proteomic approach to identify potentially bioactive peptides. Further, the effects of WPI, CNP, and CTR retentate on cell metabolic activity and on mucus production (MUC5AC and MUC2 gene expression) were assessed in intestinal goblet HT29-MTX-E12 cells. Results showed that WPI permeate induced a significant ACE1-I inhibitory effect [49.2 ± 0.64% (SEM)] compared with undigested WPI, CNP permeate, and retentate or CTR permeate (10.40 ± 1.07%). A significant increase in AOX (1.58 ± 0.04 and 1.61 ± 0.02 µmol of trolox AOX equivalents per mg of protein, respectively) upon digestion was found in WPI. Potentially bioactive peptides associated with ACE1-I and antihypertensive effects were identified in WPI permeate and CNP retentate. At specific concentrations, WPI, CNP, and CTR retentate were able to stimulate metabolic activity in HT29-MTX-E12 cells. Expression of MUC5AC was increased by CNP retentate and unaltered by WPI retentate; MUC2 expression was significantly increased by 0.33 mg/g of CNP and reduced by 1.33 mg/g of CNP. Our results confirm that milk proteins may be rich sources of bioactive compounds, with the greatest beneficial potential of CNP at the intestinal goblet cell level.

Postprandial Effects of a Proprietary Milk Protein Hydrolysate Containing Bioactive Peptides in Prediabetic Subjects.

Milk proteins have been hypothesized to protect against type 2 diabetes (T2DM) by beneficially modulating glycemic response, predominantly in the postprandial status. This potential is, amongst others, attributed to the high content of whey proteins, which are commonly a product of cheese production. However, native whey has received substantial attention due to its higher leucine content, and its postprandial glycemic effect has not been assessed thus far in prediabetes. In the present study, the impact of a milk protein hydrolysate of native whey origin with alpha-glucosidase inhibiting properties was determined in prediabetics in a randomized, cross-over trial. Subjects received a single dose of placebo or low- or high-dosed milk protein hydrolysate prior to a challenge meal high in carbohydrates. Concentration–time curves of glucose and insulin were assessed. Incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by low-dosed milk peptides compared to placebo (p = 0.0472), and a minor insulinotropic effect was seen. A longer intervention period with the low-dosed product did not strengthen glucose response but significantly reduced HbA1c values (p = 0.0244). In conclusion, the current milk protein hydrolysate of native whey origin has the potential to modulate postprandial hyperglycemia and hence may contribute in reducing the future risk of developing T2DM.