Abstract: BACKGROUND: Exercise has been widely recognized in the prevention and treatment of diabetes. Aerobic exercise has become an important part of the treatment of type 1 diabetes. However, the effect of treadmill exercise on the metabolism and chronic neuroinflammation of type 1 diabetes in different sexes needs further discussion.
OBJECTIVE: To study the effects of treadmill exercise on metabolism and chronic neuroinflammation in type 1 diabetes mice of different sexes.
METHODS: Forty C57BL/6 mice were divided into male group and female group, with 20 mice in each group. Then, a diabetes model was established by continuous injection of streptozotocin at 80 mg/kg for 3 days. Ten rats from each group were randomly selected to perform 6-week treadmill exercise as the diabetes+exercise group and another 10 rats from each group were selected as the diabetes group. Serum sex hormones, liver tissue oxidative stress, brain tissue inflammatory factors, and liver pathology were detected, and Morris water maze was performed for the observation of behavioral changes in mice.
RESULTS AND CONCLUSION: Compared with the diabetes group, the diabetes+exercise group delayed the rise of blood sugar in type 1 diabetes mice (P < 0.05) and showed a significant reduction in serum follicle-stimulating hormone, luteinizing hormone, liver superoxide dismutase, malondialdehyde, brain tumor necrosis factor α, interleukin-6 and interleukin-1β  levels (P < 0.01), while serum estradiol, progesterone, estrogen, and liver glutathione peroxidase protein levels were significantly increased (P < 0.01, P < 0.05). Compared with male type 1 diabetes mice, female type 1 diabetes mice had significantly higher estradiol levels and lower luteinizing hormone levels (P < 0.05). Compared with the male diabetes+exercise group, the female diabetes+exercise group had lower liver glutathione peroxidase levels (P < 0.05). Compared with type 1 diabetes mice, the escape latency of exercise training mice was shorter (P < 0.01). In male mice, exercises significantly increased the time and platform crossing times of type 1 diabetes mice in the target quadrant (P < 0.01 or P < 0.05), while in female mice, exercises significantly increased the time of type 1 diabetes mice in the target quadrant (P < 0.05). Correlation analysis results showed that the levels of follicle-stimulating hormone, luteinizing hormone, progesterone, superoxide dismutase, malondialdehyde, tumor necrosis factor α, and interleukin-6 were positively correlated with the level of interleukin-1β (P < 0.05 or P < 0.01), whereas the levels of estradiol and progesterone were negatively correlated with the levels of superoxide dismutase, malondialdehyde, tumor necrosis factor α, interleukin-6 and interleukin-1β (P < 0.05 or P < 0.01). Overall, there are sex differences in the effects of treadmill exercise on metabolic indicators and chronic neuroinflammatory regulation in diabetes mice. Sex hormones are an important variable of treadmill exercise in the metabolic, inflammatory and cognitive responses in diabetes mice.

Key words: treadmill exercise, type 1 diabetes, metabolism, chronic neuroinflammation, sex difference, oxidative stress, sex hormone, Morris water maze, cognition, liver dysfunction