title: The influence of high glucose and high insulin on mechanisms controlling cell cycle progression and arrest in mouse C2C12 myoblasts: the comparison with IGF-I effect.
abstract: BACKGROUND
  Myogenesis is susceptible to the availability of nutrients and humoral factors and suboptimal fetal environments affect the number of myofibers and muscle mass.
  
  
  OBJECTIVE
  We examined the mechanisms regulating cell cycle progression and arrest in skeletal myoblasts.
  
  
  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.
authors.affiliation: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences (SGGW), Nowoursynowska 159, 02-776, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Grabiec
authors.forename: M
authors.initials: M
authors.lastname: Gajewska
authors.forename: M
authors.initials: M
authors.lastname: Milewska
authors.forename: M
authors.initials: M
authors.lastname: Błaszczyk
authors.forename: K
authors.initials: K
authors.lastname: Grzelkowska-Kowalczyk
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D047468:Immunoprecipitation; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013549:Sweetening Agents; D007334:Insulin-Like Growth Factor I; D005947:Glucose