Induced oxidative eustress stimulates glucose uptake in C2C12 myotubes and skeletal muscle fibres

Abstract

Oxidative eustress -moderate intracellular levels of Reactive Oxygen and Nitrogen Species (RONS)- plays an important role modulating redox signalling processes in the cell. Glucose is vital in cells since this molecule provides the energy to maintain essential cellular functions. The reviewed literature supports that the balance and concentration of RONS affect glucose uptake in skeletal muscle. AMPK and AKT are proteins involved in signaling pathways that regulate glucose uptake. Their phosphorylation evokes the translocation of glucose transporter GLUT4 from cytosolic vesicles to the plasma membrane, enabling glucose internalization into the cells. Using methodology previously developed and validated in our laboratory – quantitative fluorescence microscopy, immunocytochemistry, and protein immunodetection –, we have explored how RONS homeostasis modulates signaling pathways. These pathways, mediated by AMPK and AKT phosphorylation, promotes GLUT4 translocation, which facilitates glucose uptake and internalization in skeletal muscle cells (myotubes and fibres). The results showed that a pro-oxidative intracellular redox environment evoked by RONS, potentially linked with oxidative eustress, activates signalling pathways (P-AMPK or P-AKT), GLUT-4 translocation from cytosol to plasma membrane and, consequently, an increase in glucose uptake. In conclusion, the RONS-induced phosphorylation of AMPK and AKT proteins improves glucose uptake in C2C12 myotubes and single skeletal muscle fibres. In perspective, our findings would lead a potential therapeutic advance that overcome the impairment to internalize glucose in the cell -insulin resistance- onset in disorders such as diabetes and obesity, and in ageing.