Effects of combined treatment with blood flow restriction and low-intensity electrical stimulation on diabetes mellitus-associated muscle atrophy in rats

Background Diabetes mellitus (DM) results in decreased muscle mass and harmful complications. Blood flow restriction (Bfr) and electrical stimulation (ES) increase muscle protein synthesis. We hypothesized that combined Bfr and low-intensity ES may be more effective in preventing diabetes-associated muscle atrophy by inhibiting the downregulation of protein synthesis-related pathways. In this study, the effects of combined Bfr and low-intensity ES on diabetes-associated muscle atrophy were investigated by evaluating advanced glycation end-products (AGEs) and receptor for AGEs (RAGE) in rats. Methods Twenty-four Goto-Kakizaki (GK) rats were randomly divided into four treatment groups: sedentary DM, DM + Bfr (pressure cuffs placed around the thigh), DM + ES, and DM + Bfr + ES. Six Wistar rats were used as an age-matched control. Levels of AGEs and the expression of RAGE, extracellular signal-regulated kinase (ERK), and ribosomal protein S6 (rpS6) were determined in plantaris muscles. Results Diabetes resulted in a loss of muscle mass and upregulation of AGEs and RAGE in the plantaris muscle compared with the control group. Treatment with Bfr and ES alone failed to attenuate diabetes-associated loss of muscle mass, and could not prevent the upregulation of AGEs. However, the combination of Bfr and ES prevented the diabetes-associated decrease in muscle mass and upregulation of AGEs. In addition, the combination treatment prevented diabetes-associated decreases in the expression of phosphorylated rpS6. Conclusions Combination treatment with Bfr and ES may prevent diabetes-associated muscle atrophy by upregulating inhibition of AGEs, which leads to the activation of protein synthesis.