Abstract

Background: Modification of the mechanisms that determine skeletal muscle mass through extracellular factors acting during fetal and postnatal period plays an essential role in health status in later life. In the present study the mechanisms controlling cell proliferation in skeletal myoblasts were examined.

Methods: Mouse C2C12 myoblasts were subjected to proliferation in the presence of high glucose (HG, 15 mmol/l). Cellular content and localization of cyclins stimulating cell cycle progression and proteins essential for cell cycle arrest were assessed by immunoblotting and immunofluorescence/confocal microscopy. The results were evaluated using Student t-test and the criterion for statistical significance was P<0.05.

Results: High glucose significantly augmented myoblast number and increased cellular level of cyclin A, cyclin B1 and cyclin D1. Nuclear localization of cyclin A and D1, and the level of cyclin D1 complexed with cyclin-dependent kinase-4 were increased by high glucose. Cellular levels of pRb and MyoD were increased by high glucose; however these proteins were localized primarily in the cytoplasm of proliferating myoblasts.

Conclusion: Stimulation of C2C12 myoblasts proliferation by high glucose is associated with: i) increase of cyclin A and cyclin D1 in myoblast nuclei, and formation of cyclin D1-cdk4 complexes, ii) decrease of pRb and MyoD nuclear localization. High ambient glucose can therefore affect the number of cells contributing to muscle fiber formation.