期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 61, 期 2, 页码 -出版社
WILEY
DOI: 10.1002/mnfr.201600301
关键词
Akt; AMPK; Casein glycomacropeptide; HepG2 cells; Insulin resistance
资金
- National Natural Science Foundation of China [31371753]
- Open Funding Project of Key Laboratory of Space Nutrition and Food Engineering [SNFE-KF-15-01]
- Key Projects in the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period [2013BAD18B12-05]
- National Dairy Industry Technology System-Beijing Innovation Team (NDITS-BIT)
ScopeRecently, casein glycomacropeptide (GMP)-derived peptide was found to possess potent antioxidant and anti-inflammatory activities. In this study, the improvement effects and underlying molecular mechanisms of GMP-derived peptide on hepatic insulin resistance were investigated. Methods and resultsThe peptide IPPKKNQDKTE was identified from GMP papain hydrolysates by LC-ESI-MS/MS. Effects of IPPKKNQDKTE on glucose metabolism and expression levels of the hepatic insulin signaling proteins in high glucose-induced insulin-resistant HepG2 cells were evaluated. Results showed that IPPKKNQDKTE dose-dependently increased glucose uptake and intracellular glycogen in insulin-resistant HepG2 cells without affecting cell viability. IPPKKNQDKTE increased the phosphorylation of Akt and GSK3 and decreased the expression levels of p-GS, G6Pase and PEPCK. These IPPKKNQDKTE-mediated protection effects were reversed by PI3K/Akt inhibitor LY294002, showing the mediatory role of PI3K/Akt. Moreover, treatment with IPPKKNQDKTE reduced IRS-1 Ser307 phosphorylation and increased phosphorylation of AMPK. Knockdown AMPK using siRNA in HepG2 cells increased Ser307 phosphorylation of IRS-1 and reduced Akt phosphorylation in IPPKKNQDKTE-treated insulin-resistant cells. ConclusionIPPKKNQDKTE prevents high glucose-induced insulin resistance in HepG2 cells by modulating the IRS-1/PI3K/Akt signaling pathway through AMPK activation, indicating that IPPKKNQDKTE plays a potential role in the prevention and treatment of hepatic insulin resistance and type 2 diabetes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据