C2C12 cell model: its role in understanding of insulin resistance at the molecular level and pharmaceutical development at the preclinical stage

Abstract

Objectives The myoblast cell line, C2C12, has been utilised extensively in vitro as an examination model in understanding metabolic disease progression. Although it is indispensable in both preclinical and pharmaceutical research, a comprehensive review of its use in the investigation of insulin resistance progression and pharmaceutical development is not available. Key findings C2C12 is a well-documented model, which can facilitate our understanding in glucose metabolism, insulin signalling mechanism, insulin resistance, oxidative stress, reactive oxygen species and glucose transporters at cellular and molecular levels. With the aid of the C2C12 model, recent studies revealed that insulin resistance has close relationship with various metabolic diseases in terms of disease progression, pathogenesis and therapeutic management. A holistic, safe and effective disease management is highly of interest. Therefore, significant efforts have been paid to explore novel drug compounds and natural herbs that can elicit therapeutic effects in the targeted sites at both cellular (e.g. mitochondria, glucose transporter) and molecular level (e.g. genes, signalling pathway). Summary The use of C2C12 myoblast cell line is meaningful in pharmaceutical and biomedical research due to their expression of GLUT-4 and other features that are representative to human skeletal muscle cells. With the use of the C2C12 cell model, the impact of drug delivery systems (nanoparticles and quantum dots) on skeletal muscle, as well as the relationship between exercise, pancreatic b-cells and endothelial cells, was discovered. Applications and role of C2C12 skeletal muscle Chun Y. Wong et al.

Insulin and IGF-1 receptors regulate complex I–dependent mitochondrial bioenergetics and supercomplexes via FoxOs in muscle

“…To develop a cell model for insulin regulation of mitochondrial function and mitophagy, we used C2C12 mouse skeletal muscle derived cell lines, which has been extensively used to study metabolic diseases (37). C2C12 myotubes were pre-treated with or without insulin and CCCP (Carbonyl cyanide m-chlorophenylhydrazone, a known mitophagy inducer) for 4 hours on day 7 of differentiation, prior to metabolic analysis using the seahorse XF24 analyzer.…”

Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models

“…In the past two decades, myoblast cell lines have been recognized as valuable experimental tools in several conditions including obesity, diabetes, and insulin resistance [97]. Both C2C12 and L6 myoblasts are able to undergo differentiation into elongated myotubes, expressing the insulin responsive glucose transporter 4 (GLUT-4) protein, which promotes insulin-stimulated glucose uptake [98,99].…”

The Molecular Mechanisms of Hypoglycemic Properties and Safety Profiles of Swietenia Macrophylla Seeds Extract: A Review

“…It is an established cellular model that can be used to elucidate many biological processes, including glucose metabolism, insulin signaling, IR, oxidative stress, reactive oxygen species (ROS), and GLUT transporters at the cellular and molecular levels. The use of the C2C12 cell line greatly supports the development of research, particularly in the drug discovery and biomedical fields, since it expresses GLUT4 and other characteristics that represent the physiology of human skeletal muscle [59], [60].…”