The diabetic phenotype is preserved in myotubes established from type 2 diabetic subjects: a critical appraisal.

Cultured human myotubes offer a unique model to distinguish between primary and environmental factors in the aetiology of insulin resistance in human skeletal muscle. The objective of this review was to summarize our and other group studies on insulin resistance in human myotubes established from lean, obese and type 2 diabetes (T2D) subjects. Overall, studies of human myotubes established from lean, obese and T2D subjects clearly show that part of the diabetic phenotype observed in vivo is preserved in diabetic myotubes. Diabetic myotubes express a primary coordinated impairment of lipid oxidation, oxidative phosphorylation (OXPHOS) and insulin-stimulated glucose metabolism. Currently, both the responsible molecular mechanisms as well as the extent to which these alterations depend on genetic and/or epigenetic alterations have yet to be identified. Based on the data, it is hypothesized that the impaired insulin-mediated glucose metabolism, impaired OXPHOS and reduced lipid oxidation observed in diabetic myotubes are caused by the reduced peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α) expression.