A milk casein hydrolysate‐derived peptide enhances glucose uptake through the AMP‐activated protein kinase signalling pathway in skeletal muscle cells
A milk casein hydrolysate‐derived peptide enhances glucose uptake through the AMP‐activated protein kinase signalling pathway in skeletal muscle cells
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牛奶酪蛋白水解物衍生肽通过 AMP 激活的蛋白激酶信号通路增强骨骼肌细胞中的葡萄糖摄取
DOI：
10.1113/ep088770
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发表时间：
2021
影响因子：
2.7
通讯作者：
W.
中科院分区：
文献类型：
--
作者：
Iwasa;M.;Takezoe;S.;Kitaura;N.;Sutani;T.;Miyazaki;H.;and Aoi;W.
新发现本研究的中心问题是什么？瑞士乳杆菌发酵乳和牛奶酪蛋白水解物（MCH）中的常见活性成分如何增强骨骼肌的葡萄糖代谢？主要发现及其重要性是什么？MCH通过刺激AMP激活的激酶而非胰岛素信号传导增强骨骼肌细胞的葡萄糖摄取。此外，MCH衍生的特异性肽Ile‐Pro‐Pro模拟了这种效果，表明MCH诱导的代谢改善的机制。摘要骨骼肌中葡萄糖代谢的改善在运动表现和预防代谢性疾病中具有关键作用。在我们以前的研究中，我们表明摄入牛奶酪蛋白水解物可以改善人体的葡萄糖代谢，但其作用机制尚未阐明。在这项研究中，我们的目的是研究牛奶酪蛋白水解物及其衍生肽对培养的骨骼肌细胞的葡萄糖摄取和葡萄糖代谢信号的作用机制。分化的C2 C12肌管用于实验。用酪蛋白水解物、缬氨酸-脯氨酸-脯氨酸和异亮氨酸-脯氨酸-脯氨酸孵育分化的细胞。随后，检查2-脱氧葡萄糖摄取率和胰岛素依赖性和非依赖性信号传导因子的磷酸化水平。我们发现，牛奶酪蛋白水解物和异亮氨酸-脯氨酸-脯氨酸处理的细胞中的2-脱氧-葡萄糖摄取速率均高于对照细胞。免疫印迹分析表明，在牛奶酪蛋白水解物和异亮氨酸-脯氨酸-脯氨酸处理的细胞中，AMP活化蛋白激酶（胰岛素非依赖性信号传导的速率限制因子）和肝激酶B1（AMP活化蛋白激酶的上游因子）的磷酸化水平均高于对照细胞。用缬氨酸-脯氨酸-脯氨酸处理后未观察到这种显著的效果。此外，在不同条件下，胰岛素依赖性信号传导未受到显著影响。我们的研究结果表明，牛奶酪蛋白水解物通过激活骨骼肌细胞中的胰岛素非依赖性AMP激活蛋白激酶信号传导来增强葡萄糖摄取，这可能是由牛奶酪蛋白水解物衍生的肽，即异亮氨酸-脯氨酸-脯氨酸介导的。
New FindingsWhat is the central question of this study?How do common active ingredients contained in bothLactobacillus helveticus‐fermented milk and milk casein hydrolysate (MCH) enhance glucose metabolism by skeletal muscle?What is the main finding and its importance?MCH enhanced glucose uptake in skeletal muscle cells by stimulating AMP‐activated kinase, but not insulin, signalling. Moreover, the MCH‐derived specific peptide Ile‐Pro‐Pro mimicked this effect, suggesting a mechanism for MCH‐induced metabolic improvement.AbstractImprovement 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 valine–proline–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 AMP‐activated protein kinase signalling in skeletal muscle cells, which might be mediated by a milk casein hydrolysate‐derived peptide, namely, isoleucine–proline–proline.
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影响因子：
3.3
作者：
Blake B. Rasmussen;Chad R. Hancock;W. Winder
通讯作者：
Blake B. Rasmussen;Chad R. Hancock;W. Winder
酸奶对艾利希腹水肿瘤细胞增殖的抑制作用。
DOI：
--
发表时间：
1973
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
G. V. Reddy;K. Shahani;M. Banerjee
通讯作者：
M. Banerjee
呫吨衍生物通过激活 LKB1 依赖性 AMP 激活蛋白激酶来增加葡萄糖利用率
影响因子：
3.7
作者：
Yonghoon Kwon;Parkyong Song;J. Yoon;Jaewang Ghim;Dayea Kim;B. Kang;Taehoon G. Lee;Jin;Joong;I. Youn;Hyeongjoo Lee;S. Ryu
通讯作者：
S. Ryu
DOI：
10.1152/ajpendo.1995.268.5.e987
发表时间：
1995-05-01
影响因子：
5.1
作者：
GOODYEAR, LJ;GIORGINO, F;SMITH, RJ
通讯作者：
SMITH, RJ
影响因子：
--
作者：
CARTEE, GD;YOUNG, DA;HOLLOSZY, JO
通讯作者：
HOLLOSZY, JO