Department of Geriatrics, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, PR China.
Department of Geriatrics, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, PR China.
Arch Gerontol Geriatr. 2024 Sep;124:105462. doi: 10.1016/j.archger.2024.105462. Epub 2024 Apr 26.
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.
本研究旨在探讨胰高血糖素样肽-2（GLP-2）对体内和体外肌肉衰老的影响。
6 周龄 C57BL/6J 小鼠腹腔注射 D-半乳糖（200mg/kg/天）8 周后，每日皮下注射 GLP-2（300 或 600μg/kg/天）4 周。采用相对握力和肌肉重量评估骨骼肌功能和质量。通过组织学分析、免疫荧光染色和 TUNEL 染色分别评估肌纤维的大小和类型以及细胞凋亡。用 D-半乳糖（40mg/ml）和 GLP-2 处理 C2C12 肌管。采用 Western blot 检测分化相关肌源性分化因子 D（MyoD）、肌细胞生成素（MyoG）和肌球蛋白重链（Myhc）、降解相关肌肉环指 1（MuRF-1）和肌肉萎缩 F 盒（MAFbx）/Atrogin-1 以及凋亡相关 B 细胞淋巴瘤 2（Bcl-2）和 Bax 的蛋白表达。应用 PI3k 抑制剂 LY294002 探讨 GLP-2 是否通过 IGF-1/PI3k/Akt/FoxO3a 信号通路调节肌生成和肌管衰老。
结果表明，GLP-2 显著逆转了 D-半乳糖诱导的小鼠肌肉重量、相对握力、肌纤维直径和横截面积下降。除了抑制肌肉和 C2C12 肌管中 MuRF-1 和 Atrogin-1 的表达外，GLP-2 还显著增加了 MyoD、MyoG 和 Myhc 的表达。GLP-2 显著抑制细胞凋亡。Western blot 分析表明，GLP-2 的调节可能归因于 IGF-1/PI3k/Akt/FoxO3a 磷酸化通路的激活。
本研究表明，GLP-2 通过 IGF-1/PI3k/Akt/FoxO3a 通路改善 D-半乳糖诱导的肌肉衰老。
