Are cultured human myotubes far from home?

Abstract

IntroductionSatellite cells can be isolated from skeletal muscle biopsies, activated to proliferating myoblast and differentiated into multinuclear myotubes in culture. These cell cultures represent an essential model system to intact human skeletal muscle, which can be modulated ex vivo. Advantages of this system include; having the most relevant genetic background to study human disease (as opposed to rodent cell cultures), the extracellular environment can be precisely controlled and the cells are not immortalized, thereby offering the possibility of studying innate characteristics of the donor. This review will focus on how human myotubes can be used as a tool to study metabolism in skeletal muscles, with a special attention to changes in muscle energy metabolism in obesity and type 2 diabetes.Limitations of this cell system and possible approaches to improve the current model will also be discussed.

Sustained Action of Ceramide on the Insulin Signaling Pathway in Muscle Cells: IMPLICATION OF THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE

“…This model is attractive because it offers enough material to study insulin signaling in vitro in cells that display several characteristics of mature human skeletal muscle. Indeed, myotubes established from patients with type 2 diabetes have been shown to maintain their metabolic phenotype in culture (42). Using this model, we show that PKR mRNA and expression levels and PKR autophosphorylation are enhanced compared with myotubes from control patients.…”

Resistance to the Beneficial Effects of Exercise in Type 2 Diabetes: Are Some Individuals Programmed to Fail?

“…These models also allow for the use of genetic, pharmacological, and physiological manipulations to investigate mechanisms of the responses observed in vivo in humans (reviewed in Ref. 60). …”

Myotubes from lean and severely obese subjects with and without type 2 diabetes respond differently to an in vitro model of exercise

“…However, a combination of genetic and epigenetic mechanisms is probably involved, and this has been reviewed in a recent paper (1). For example, epigenetic regulation of skeletal muscle stem cells and skeletal muscle differentiation, exercise, diet, and a family history of T2D have all been described to influence DNA methylation in human skeletal muscle, and these are traits that might follow the isolated satellite cells into their corresponding cultured myotubes (1).…”

“…Human myotubes are considered a valid model for studying metabolic disorders as obesity and T2D because perturbances evident in vivo, such as depressed lipid oxidation and insulin resistance, are retained in myotubes in culture (1,7,19). After EPS, myotubes established from lean nondiabetic subjects showed an increase in glucose and lipid metabolism as well as indications of fast-twitch glycolytic muscle fiber transformation into slow-type oxidative fibers (36) and enhanced expression and release of IL-6 and IL-8 (31,44,48).…”