This study aimed to investigate the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on glucose metabolism in skeletal muscle of T2DM mice, and to explore the potential regulatory mechanisms of MSTN-AMPK/PGC-1α signaling on mitochondrial quality control and its relationship with glucose metabolism.
Male db/db mice at 8 weeks of age were adaptively fed for 7 days and then randomly assigned to three parallel experimental groups: diabetic control group (DC), moderate-intensity continuous training group (MICT), and high-intensity interval training group (HIIT). Age-matched wild-type (db/m) mice were used as the normal control group (NC), with each experimental group consisting of 12 biological replicates.
Body Weight: From week 0 to week 10, the body weight of the DC group was significantly higher compared to the NC group (P < 0.001). Compared to the DC group, both the MICT and HIIT groups showed a significant decrease in body weight starting from week 4 (P < 0.05). There was no significant difference in body weight between the HIIT and MICT groups.
Random Blood Glucose Levels: From week 0 to week 10, the random blood glucose levels of the DC group were significantly higher compared to the NC group (P < 0.001). Compared to the DC group, both the MICT and HIIT groups showed a significant decrease in blood glucose levels starting from week 6 (P < 0.05, P < 0.01). There was no significant difference in blood glucose levels between the HIIT and MICT groups during the 10-week intervention period.
Cross-Sectional Area (CSA) of Muscle Fibers: Statistical analysis revealed that the CSA of the DC group was significantly lower compared to the NC group (P < 0.001). Compared to the DC group, both the MICT and HIIT groups showed a significant increase in CSA (P < 0.05). The CSA of the HIIT group was significantly higher compared to the MICT group (P < 0.05).
Glycogen Content: The glycogen content in the DC group was significantly lower compared to the NC group (P < 0.001). Compared to the DC group, both the MICT and HIIT groups showed a significant increase in glycogen content (P < 0.001). The glycogen content in the HIIT group was significantly higher compared to the MICT group (P < 0.001).
Glucose Metabolism-Related Indicators in Skeletal Muscle: The protein expression of GLUT4 in the DC group was significantly lower compared to the NC group (P < 0.01). Compared to the DC group, both the MICT and HIIT groups showed a significant increase in GLUT4 protein expression (P < 0.001).
Protein Expression and Phosphorylation Levels: Compared to the NC group, the protein expression of PGC-1α and AMPK, as well as the phosphorylation level of AMPK, were significantly lower in the DC group (P < 0.001, P < 0.01), while the protein expression of MSTN was significantly higher (P < 0.01). Compared to the DC group, both the MICT and HIIT groups showed a significant increase in PGC-1α protein expression and AMPK phosphorylation level (P < 0.01, P < 0.001), and a significant decrease in MSTN protein expression (P < 0.001). The protein expression of AMPK did not change significantly in the MICT group but increased significantly in the HIIT group (P < 0.001). Compared to the MICT group, the HIIT group showed a significant increase in PGC-1α and AMPK protein expression, as well as AMPK phosphorylation level (P < 0.01, P < 0.05), while the protein expression of MSTN did not change significantly.
Conclusion: Both high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) effectively alleviated glucose metabolism abnormalities in T2DM mice, as evidenced by improvements in body weight, blood glucose levels, and skeletal muscle glucose metabolism function, and an enhancement in skeletal muscle mitochondrial quality. Additionally, HIIT demonstrated superior intervention effects on mitochondrial quality control compared to MICT.
High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) improved glucose metabolism disorders in T2DM skeletal muscle by inhibiting MSTN expression, activating the AMPK/PGC-1α signaling axis, and enhancing mitochondrial quality control.
