Background: Myogenesis is susceptible to the availability of nutrients and humoral factors and suboptimal fetal environments affect the number of myofibers and muscle mass.
Aim: We examined the mechanisms regulating cell cycle progression and arrest in skeletal myoblasts.
Materials and methods: Mouse C2C12 myoblasts were subjected to proliferation or induction of differentiation in the presence of high glucose and high insulin (HGHI glucose 15 mmol/l, insulin 50 nmol/l), and these effects were compared with the influence of anabolic factor for skeletal muscle, insulin-like growth factor-I (IGF-I 30 nmol/l).
Results: High glucose and high insulin, similarly to IGF-I, increased the intracellular level of cyclin A, cyclin B1 and cyclin D1 during myoblast proliferation. In HGHI-treated myoblasts, these cyclins were localized mostly in the nuclei, and the level of cdk4-bound cyclin D1 was augmented. HGHI significantly stimulated the expression of cyclin D3, total level of p21 and cdk-bound fraction of p21 in differentiating cells. The cellular level of MyoD was augmented by HGHI both in proliferating and differentiating myogenic cells.
Conclusions: High glucose and insulin modify the mechanisms controlling cell cycle progression and the onset of myogenesis by: (1) increase of cyclin A, cyclin B1 and cyclin D1 in myoblast nuclei, and stimulation of cyclin D1-cdk4 binding; (2) increase in cyclin D3 and MyoD levels, and the p21-cdk4 complexes after induction of differentiation. Hyperglycemia/hyperinsulinemia during fetal or postnatal life could exert effects similar to IGF-I and can be, therefore, favourable for skeletal muscle growth and regeneration.