This study was funded by grants from Science for Life Laboratory Stockholm, by the ProNova VINN Excellence Centre for Protein Technology (VINNOVA, Swedish Governmental Agency for Innovation Systems), by grants from the Knut and Alice Wallenberg Foundation and the European Union 6th Framework P-Mark (Grant number LSHC-CT-2004-503011), Swedish Cancer Society, Sotrastaurin research buy and Swedish Research Council Medicine (VR). “
“Type 2 diabetes (T2D) is a metabolic disease characterized by derangements in glucose and lipid homeostasis in insulin-sensitive organs such as liver [1], adipose tissue [2] and skeletal muscle [3].

Skeletal muscle accounts for over 80% of insulin-stimulated glucose uptake, and impairments in insulin action on non-oxidative glucose metabolism in this tissue are among the earliest metabolic defects in T2D [4]. Substantial evidence from proteomic and genomic studies suggests that metabolic defects exist in skeletal muscle from people with T2D versus normal glucose tolerance (NGT) [5], [6], [7], [8], [9] and [10]. A broad spectrum of cellular defects, including mitochondrial function, fatty acid metabolism and inflammation have ABT-199 solubility dmso been observed in skeletal muscle

from T2D patients [11] and [12]. Due to the complexity of T2D, greater insight into mechanisms underlying the development of skeletal muscle insulin resistance is warranted, due to the important role of this tissue in the maintenance of whole body glucose, amino acid and lipid homeostasis [13], [14] and [15]. T2D and related metabolic diseases impart a coordinated, progressive dysfunction in skeletal muscle that is manifested through alterations in both local gene

transcription [16] and circulating metabolites and hormones [17] and [18]. Thus, the inter-individual variation, and the influence of external systemic factors such as hormones, cytokines and metabolites, which may influence the identification of inherent T2D-related differences, Resveratrol must be taken into consideration when performing a global profiling of proteins in skeletal muscle to detect T2D-specific signatures. Primary differentiated myotubes display many features of mature skeletal muscle [19]. Thus culturing satellite cells has become a useful research model to study molecular mechanisms underlying cellular and physiological processes such as cell growth, differentiation, apoptosis and the regulation of specific gene expression in skeletal muscle. In spite of the non-similarity to a whole mature muscle phenotype, differentiated human myotubes may also maintain the diabetic phenotype, as evidenced by impaired glucose metabolism and insulin action [7], [20] and [21]. Another advantage of primary differentiated myotube cultures is the higher protein extraction yield acquired from cells verses the amount typically obtained from small muscle biopsies.