Our findings indicate that epigenetic or genetic changes imprinted in the T2D myotubes may increase abundance of proteins involved in mitochondrial function and energy metabolism. Increased oxidative stress and damage has been observed in skeletal muscle from T2D patients [46]. Whether the oxidative defense system is defective in skeletal

muscle from T2D patients is unclear. In our analysis of myotubes derived from T2D selleck screening library patients versus NGT subjects, several proteins involved in the oxidative stress response and mitochondrial reactive oxygen species (ROS) production were downregulated. The glutathione S-transferase proteins (GSTT1, GSTP1, GSTM2) associated with the NRF2 system were less abundant in myotubes from T2D. GST proteins are induced by NRF2 activation to detoxify electrophilic compounds,

including products of oxidative stress by conjugation with glutathione [47]. Thus, reduced GST protein abundance in T2D may lead to a disturbed oxidative stress defense. Glutathione is the major endogenous antioxidant which plays a role in disease prevention [48]. Levels of glutathione in blood are reduced in diabetes [46], [49] and [50] We therefore investigated whether the proteome data on GST proteins is mirrored by changes in glutathione levels. We found that the total glutathione content was reduced in T2D-derived cells. These changes Galunisertib in protein levels and total glutathione content could either indicate that the oxidative defense system is reduced, increasing susceptibility of T2D myotubes to oxidative stress, or that the NRF2 system has coordinately adapted to lower oxidative stress in T2D muscle. Whether the reduced levels of glutathione and GST protein contents in myotubes derived from T2D patients contributes

to metabolic disorders, in connection with increased ROS production and oxidative damage, Nabilone requires further investigation. A coordinated decrease in protein content of several heat shock proteins (HSP90A, HSPB1, PPIA) was observed in myotubes derived from T2D patients. In addition to protein folding and unfolding, several heat shock proteins have multifunctional roles. For example, HSP90A plays a key role in endoplasmic reticulum stress response and protein ubiquitin-proteasome system (UPS) [51], whereas HSPB1 is involved in Akt activation, UPS, stress resistance and actin organization [52]. Furthermore, HSPB1 is suggested to play an important role in insulin resistance [53], lipid metabolism and regulation of metabolically active enzymes. The decreased abundance of heat shock proteins in T2D myotubes is consistent with the hypothesis that loss of homeostatic signaling may lead to a inflammation, T2D [54] and aging [55].