Abstract
BACKGROUND/OBJECTIVES: Skeletal muscle plays a pivotal role in whole-body glucose metabolism and is a major target in the pathogenesis and treatment of insulin resistance and type 2 diabetes. The C2C12 myotube cell line is one of the most used in vitro models to investigate mechanisms of insulin resistance. This systematic review (1) summarizes the most common experimental conditions including palmitate concentrations and treatment durations used to induce insulin resistance in C2C12 myotubes; (2) characterizes outcomes related to insulin resistance; and (3) discusses strengths and limitations associated with this model. METHODS: A systematic search of PubMed and Scopus was conducted using terms "C2C12 AND palmitate AND insulin resistance" and related variations. A total of 191 articles met inclusion criteria. RESULTS: The most frequently used palmitate concentrations were 0.25 mM, 0.5 mM, and 0.75 mM for at least 16 h, which consistently led to decreased insulin-stimulated pAkt expression, GLUT4 abundance, and insulin-stimulated glucose uptake. CONCLUSIONS: The high volume and consistency of primary findings is a key strength of this article which demonstrated reduced insulin signaling across various culture conditions, treatment durations, and insulin co-stimulation protocols.