1. GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice.
- Author
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Ye, Yang-Li, Kuai, Zheng, Qian, Dian-Dian, He, Yu-Ting, Shen, Ji-Ping, Wu, Ke-Fen, Ren, Wei-Ying, and Hu, Yu
- Subjects
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PROTEINS , *IN vitro studies , *SKELETAL muscle , *PHOSPHORYLATION , *APOPTOSIS , *CELLULAR signal transduction , *IN vivo studies , *FLUORESCENT antibody technique , *GLUCAGON-like peptides , *CELL lines , *MICE , *GENE expression , *AGING , *ANIMAL experimentation , *HISTOLOGICAL techniques , *WESTERN immunoblotting , *STAINS & staining (Microscopy) , *GRIP strength - Abstract
• GLP-2 ameliorated D-galactose induced muscle atrophy in mice. • GLP-2 promoted protein synthesis and alleviated protein degradation and apoptosis. • The IGF-1/PI3K/Akt/FoxO3 pathway played a role in the protective effect of GLP-2. The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro. Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 μg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway. The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway. This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2024
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