A milk casein hydrolysate‐derived peptide enhances glucose uptake through the AMP‐activated protein kinase signalling pathway in skeletal muscle cells

Abstract

Improvement of glucose metabolism in the skeletal muscle has a key role in exercise performance and prevention of metabolic diseases. In our previous study, we showed that intake of milk casein hydrolysate improves glucose metabolism in humans, but the mechanism of action was not elucidated. In this study, we aimed to investigate the mechanism of action of milk casein hydrolysate and its derived peptides on glucose uptake and glucose metabolic signalling in cultured skeletal muscle cells. Differentiated C2C12 myotubes were used for the experiments. The differentiated cells were incubated with milk casein hydrolysate, valine-proline-proline and isoleucine-proline-proline. Subsequently, the rate of 2-deoxy-glucose uptake and the phosphorylation levels of insulin-dependent and-independent signalling factors were examined. We found that the rate of 2-deoxy-glucose uptake in both milk casein hydrolysate and isoleucine-proline-proline-treated cells was higher than that in the control cells. Immunoblotting assays showed that the phosphorylation levels of AMP-activated protein kinase, a rate-limiting factor in insulin-independent signalling, and of liver kinase B1, an upstream factor of AMP-activated protein kinase, in both milk casein hydrolysate and isoleucine-proline-proline-treated cells were higher than those in the control cells. Such significant effects were not observed after treatment with valineproline-proline. Moreover, the insulin-dependent signalling was not significantly affected under the different conditions. The findings of our study suggest that milk casein hydrolysate enhances glucose uptake by activating insulin-independent AMPactivated protein kinase signalling in skeletal muscle cells, which might be mediated by a milk casein hydrolysate-derived peptide, namely, isoleucine-proline-proline.

In Vitro and in Silico Analyses of the Adiponectin Receptor Agonistic Action of Soybean Tripeptides

“…Various food-derived compounds involving biologically active peptides have displayed physiological functions that are potentially valuable in managing and preventing NIDDM. , Several good candidate antidiabetic food compounds have been described. These include the WH dipeptide that activates peptide/histidine transporter 1 (PHT1)-mediated liver kinase B1 (LKB1)/AMPK/Glut4 translocation, tripeptide IPP that activates LKB1/AMPK/Glut4 translocation, and cereal tripeptides that include IQP, IPQ, VEP, and VPE, which activate insulin-independent AMPK/Glut4 translocation. However, the mechanism by which these peptides activate signaling for Glut4 translocation remains unclear.…”

The Degree of Hydrolysis and Peptide Profile Affect the Anti-Fatigue Activities of Whey Protein Hydrolysates in Promoting Energy Metabolism in Exercise Mice

“…Previous studies demonstrated that whey hydrolysate, casein hydrolysate, and BCAA-containing peptides can increase the glucose uptake activity and glycogen synthesis rate in skeletal muscle cells. 32,33 Both plasma glucose and muscle glycogen are important fuels for maintaining muscle activity during exercise. 34 However, the glucose content in H-AXH was the lowest and we hypothesized that the uptake of glucose in muscle cells leads to the decrease in plasma glucose, and relevant mechanisms would be further explored.…”

Protein and Sport: Alternative Sources and Strategies for Bioactive and Sustainable Sports Nutrition

“…Since bioactive peptides were discovered in 1979, different biological activities have been described as antioxidant, antimicrobial, opioid, immunomodulatory, anti-inflammatory, antihypertensive, antidiabetic or hypocholesterolemic, among others (87,88). In this sense, some studies reported that certain bioactive peptides may exert a positive effect on muscle glucose uptake and glycogen restore by activating insulin-independent AMP-activated protein kinase signaling in skeletal muscle cells (89,90). Moreover, endogenous insulin appears to exert a positive effect on MPS due to their vasodilator effect by stimulating endothelial nitric oxide production, and increasing skeletal muscle glucose uptake (91).…”