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

Abstract

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.

Altered dynamics of lipid metabolism in muscle cells from patients with idiopathic inflammatory myopathy is ameliorated by 6 months of training

“…Importantly, imprinting of muscle satellite cells appears to be relatively stable, and it can persist in vitro across many passages of cells (Covington et al . 2015; Gaster, 2019). Seaborne et al .…”

“…So far, only a very limited number of studies have explored the impact of relatively short term in vivo interventions on the in vitro phenotypes of cultured muscle cells (Sparks et al 2013;Hinkley et al 2017;Lund et al 2017). Importantly, imprinting of muscle satellite cells appears to be relatively stable, and it can persist in vitro across many passages of cells (Covington et al 2015;Gaster, 2019). Seaborne et al (2018a,b) showed that even acute exercise-induced changes in methylation of specific genes related to exercise adaptive response can persist in skeletal muscle for as long as 22 weeks.…”

Glucose metabolism and metabolic flexibility in cultured skeletal muscle cells is related to exercise status in young male subjects

“…Interestingly, we and others have previously shown that cultured muscle cells generated from type 2 diabetic subjects have reduced insulin-stimulated glucose uptake and glycogen synthesis compared to cells from non-diabetics (McIntyre et al, 2004, Bakke et al, 2015, Gaster et al, 2002, and thus it is believed that the reduced insulin action results partly from genetic and partly from epigenetic changes (McIntyre et al, 2004).…”

Myokine Regulation of Insulin Secretion: Impact of Inflammation and Type 2 Diabetes

“…To that end, we employed the human SkM cell system (Henry et al, 1995). Multiple investigators have shown that human SkM satellite cells, when cultured and differentiated to myotubes display many of the properties of intact muscle, including T2D-related differences in glucose and fat metabolism (reviewed in Aas et al, 2013;Gaster, 2018), protein expression (Al-Khalili et al, 2014) and, most important to the current goals, secretory profile (Ciaraldi et al, 2016;Massart et al, 2016). Media conditioned by culture with myotubes, was taken as a surrogate for secretion into the extracellular space, and ultimately into the circulation.…”