High glucose-mediated alterations of mechanisms important in myogenesis of mouse C2C12 myoblasts

We have examined the progression and regulation of myogenesis, cellular levels of IGFBP-4, -5, -6, and several extracellular matrix (ECM) proteins (fibronectin, integrin α5, β1 subunits and a disintegrin metalloprotease ADAM12) in murine C2C12 myoblasts during 3-day differentiation under high glucose alone or combined with high insulin, factors characteristic for type 1 and 2 diabetes. High ambient glucose inhibited myogenesis of C2C12 myoblasts, an effect manifested by a twofold decrease in myoblast fusion, a drop in intracellular MyoD, myogenin and MHC levels, and increased cellular content of active myostatin isoform. Reduction in myogenesis by high glucose is accompanied by increase in cellular levels of IGFBP-4 and -6 and decrease in IGFBP-5. High glucose could modify ECM components assembly, by the increase in fibronectin levels and the decrease in metalloprotease ADAM12, without the effect on integrin α5 and β1 subunits. In contrast, high glucose and high insulin activate myoblast differentiation, manifested by an increase in fusion index and myogenin, as well as a drop in myostatin levels. The presence of high insulin prevented high-glucose-dependent changes in IGFBPs and ECM proteins. The data indicate the potential mechanisms of the influence of extracellular environment associated with maternal diabetes and insulin resistance on foetal myogenesis.