Effects of Aerobic and Interval Training on Peripheral Nerve Recovery in Male and Female Diabetic Rats

Background Diabetes mellitus negatively affects the peripheral nervous system, often leading to diabetic neuropathy (DN), which impairs nerve regeneration. Although exercise therapy promotes peripheral nerve regeneration, its effects under diabetic conditions remain unclear. The aim of this study was to investigate the effects of aerobic exercise and interval training on nerve regeneration following tibial nerve crush injury in male and female type 1 diabetic and control rats. Methods Type 1 diabetes mellitus was induced in Wistar rats via intraperitoneal injection of streptozotocin (50 mg/kg), and diabetes was confirmed after two weeks (blood glucose >400 mg/dL). Diabetic (DM) and age-matched control (CO) rats underwent tibial nerve crush injury and were randomly assigned to sedentary (SED), aerobic training (AT), or interval training (IT) groups. The AT group swam for 10 minutes, five times per week, while the IT group performed eight sets of 20-second swimming with 40-second rest intervals while carrying a weight equivalent to 18% of body weight, five times per week. Nerve recovery was assessed using compound muscle action potential (CMAP), nerve conduction velocity (NCV), and retrograde labeling of motor neurons. Results CMAP recovery rate and NCV were significantly lower in diabetic rats than in controls. In male rats, only aerobic training improved CMAP recovery rate and NCV, whereas interval training had no beneficial effects. Conversely, in female rats, both AT and IT significantly enhanced functional recovery, indicating a sex-dependent response. Motor neuron counts were lower in diabetic rats. In males, AT increased the number of motor neurons, whereas no significant changes were observed in females. Conclusion The effects of exercise on diabetic nerve regeneration are sex-dependent. In male rats, only aerobic exercise was beneficial, whereas interval training impaired recovery. In female rats, both aerobic and interval training promoted functional recovery. These findings highlight the potential of sex-specific exercise interventions for the management of DN.