Postprandial leucine and insulin responses and toxicological effects of a novel whey protein hydrolysate-based supplement in rats

Abstract

The purpose of this study was: aim 1) compare insulin and leucine serum responses after feeding a novel hydrolyzed whey protein (WPH)-based supplement versus a whey protein isolate (WPI) in rats during the post-absorptive state, and aim 2) to perform a thorough toxicological analysis on rats that consume different doses of the novel WPH-based supplement over a 30-day period. In male Wistar rats (~250 g, n = 40), serum insulin and leucine concentrations were quantified up to 120 min after one human equivalent dose of a WPI or the WPH-based supplement. In a second cohort of rats (~250 g, n = 20), we examined serum/blood and liver/kidney histopathological markers after 30 days of feeding low (1human equivalent dose), medium (3 doses) and high (6 doses) amounts of the WPH-based supplement. In aim 1, higher leucine levels existed at 15 min after WPH vs. WPI ingestion (p = 0.04) followed by higher insulin concentrations at 60 min (p = 0.002). In aim 2, liver and kidney histopathology/toxicology markers were not different 30 days after feeding with low, medium, high dose WPH-based supplementation or water only. There were no between-condition differences in body fat or lean mass or circulating clinical chemistry markers following the 30-day feeding intervention in aim 2. In comparison to WPI, acute ingestion of a novel WPH-based supplement resulted in a higher transient leucine response with a sequential increase in insulin. Furthermore, chronic ingestion of the tested whey protein hydrolysate supplement appears safe.

A Whey Protein Hydrolysate Promotes Insulinotropic Activity in a Clonal Pancreatic β-Cell Line and Enhances Glycemic Function in ob/ob Mice1–3

“…In a study involving several animal models of insulin resistance, this peptide displayed antidiabetic effects, with a suppression in the elevation of blood glucose during an oral glucose tolerance test (36). In a recent study, Toedebusch et al (37) analyzed the postprandial effects of intact (WP) and hydrolyzed WPs (WPH) in Wistar rats. Higher serum Leu and insulin concentrations were observed after a 60-min gavage with WPH compared with WP.…”

Effects of protein type and composition on postprandial markers of skeletal muscle anabolism, adipose tissue lipolysis, and hypothalamic gene expression

“…Thus, we speculate that the increase in Akt phosphorylation in the WPC and 70 W/30E groups may have been due to the superior ability of whey protein in stimulating insulin secretion and, thus, downstream insulin signaling in skeletal muscle. While we did not measure serum insulin responses in the current study, we have previously shown that WPH feeding to rats causes a robust (>2-fold) rise in insulin 60 min post-feeding [ 23 ]. Hence, foods containing a higher proportion of whey protein may stimulate greater intramuscular insulin signaling, and future research should continue to examine if WPC or WPH feeding in acute and long-term settings can enhance insulin sensitivity in insulin-resistant subjects.…”

“…Indeed, in vivo [ 19 , 20 ] and in vitro [ 21 ] evidence suggests that hydrolyzed whey or native whey protein increases the activation of postprandial intramuscular insulin signaling markers. Putative bioactive peptides from whey protein hydrolysates (WPH) have also been shown to exhibit insulin secretagogue properties versus intact whey protein [ 22 , 23 ]. Likewise, we have recently demonstrated that acute WPH feeding in rats increases the appearance of di- and oligopeptides as well as numerous lipolysis-related serum markers (i.e., epinephrine, glycerol and numerous free fatty acids) compared to an isonitrogenous WPC feeding condition [ 18 ].…”

A High Protein Diet Has No Harmful Effects: A One-Year Crossover Study in Resistance-Trained Males

“…Other work on rodents found no evidence of renal damage; however, they did find that rats receiving a high protein diet experienced renal hypertrophy [2]. Notwithstanding, a more recent rat study reported that 30 days of very high whey protein supplemented diet (i.e., 6 human-equivalent 20 g doses per day) did not adversely affect blood and/or histological markers of liver or kidney health and instead may improve liver health when compared to rats not receiving protein [3]. …”