GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice

Arch Gerontol Geriatr. 2024 Sep:124:105462. doi: 10.1016/j.archger.2024.105462. Epub 2024 Apr 26.

Abstract

Background: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro.

Methods: 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.

Results: 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.

Conclusions: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway.

Keywords: D-galactose; Glucagon-like peptide-2; Myogenesis; Skeletal muscle aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Animals
  • Apoptosis / drug effects
  • Forkhead Box Protein O3* / metabolism
  • Galactose*
  • Glucagon-Like Peptide 2* / pharmacology
  • Insulin-Like Growth Factor I* / metabolism
  • Insulin-Like Growth Factor I* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal* / drug effects
  • Muscle, Skeletal* / metabolism
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction* / drug effects

Substances

  • Galactose
  • Forkhead Box Protein O3
  • Insulin-Like Growth Factor I
  • Proto-Oncogene Proteins c-akt
  • FoxO3 protein, mouse
  • Glucagon-Like Peptide 2
  • Phosphatidylinositol 3-Kinases