The effect of chronic high insulin exposure upon metabolic and myogenic markers in C2C12 skeletal muscle cells and myotubes. Issue 7 (10th April 2018) - Turner, Mark C.
Abstract: Skeletal muscle is an insulin sensitive tissue and accounts for approximately 80% of post‐prandial glucose disposal. This study describes the effects of insulin, delivered for 72 h, to skeletal muscle myoblasts during differentiation or to skeletal muscle myotubes. After chronic treatment, cultures were acutely stimulated with insulin and analyzed for total and phosphorylated Akt (Ser 473 ), mRNA expression of metabolic and myogenic markers and insulin‐stimulated glucose uptake. Skeletal muscle cells differentiated in the presence of insulin chronically, reduced acute insulin stimulated phosphorylation of Akt Ser 473 . In addition, there was a reduction in mRNA expression of Hexokinase II (HKII), GLUT4 and PGC‐1α. Insulin‐stimulated glucose uptake was attenuated when cells were differentiated in the presence of insulin. In contrast, myotubes exposed to chronic insulin showed no alterations in phosphorylation of Akt Ser 473 . Both HKII and GLUT4 mRNA expression were reduced by chronic exposure to insulin; while PGC‐1α was not different between culture conditions and was increased by acute insulin stimulation. These data suggest that there are differential responses in insulin signalling, transcription, and glucose uptake of skeletal muscle cells when cultured in either the presence of insulin during differentiation or in myotube cultures. Abstract : Skeletal muscle cells were cultured in the presence of insulin to investigate its effects upon insulin signalling and glucose uptake. Skeletal muscle cells differentiated in the presence of insulin showed the greatest changes in insulin signalling and glucose uptake. Therefore, differentiating skeletal muscle cells with insulin during differentiation results in an insulin insensitive model which can be further applied to investigate potential therapies for treating insulin resistance.