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.