Aerobic Exercise Training Improves Skeletal Muscle Mitochondrial Function In Type 2 Diabetic Model

Abstract

Type-2 diabetes mellitus (T2DM) severely affects skeletal muscle metabolism, especially the mitochondrial function. The mechanism of exercise-induced improvement in mitochondrial function underlying skeletal muscle-related T2DM changes is unclear. PURPOSE: To determine the effects of aerobic exercise training on exercise capacity and skeletal muscle mitochondrial function in the diabetes spontaneous mutation model (Leprdb). METHODS: 12-week-old male diabetic B6 db mice (db/db, n = 23) and control (db+/-, n = 23) were divided into four groups; db/+ CON, db/+ Ex, db/db CON, and db/db Ex. 8-weeks of exercise (5-times/week, 50 min/day, 12-15 m/min) was performed in db/+ Ex and db/db Ex. All groups were measured grip strength, muscle fatigue, and conducted rota-rod test and maximal-aerobic-running-capacity. After 8-weeks, the muscle fibers of soleus (SOL) and gastrocnemius (GAS) were collected and analyzed for mitochondrial O2, H2O2, and Ca2+ capacity. RESULTS: The SOL in the db/db Ex was higher in muscle mass than db/db CON (5.7 ± .4vs. 4.23 ± .2, p < .05). The GAS in the db/db Ex group was lower in muscle mass than db/+ CON (85.3 ± 3.6 vs.137.4 ± 4.4, p < .05). Grip strength (41.4 ± 1.5 vs. 31.8 ± 1.5, p < .05), muscle fatigue index (30.2 ± 1.3 vs. 39.7 ± 1.5, p < .05), rota-rod test (30.4 ± 1.8 vs. 19.6 ± 1.3, p < .05), and maximal running capacity (18.9 ± 1.4 vs. 12.6 ± 0.2, p < 0.05) in db/db Ex were higher than the db/db CON. Mitochondrial O2 consumption at ADP-stimulated maximal respiration of complex I substrates in both SOL (55.3 ± 2.6 vs. 24.8 ± 2.1, p < 0.05) and GAS (40.3 ± 1.7 vs. 24.1 ± 2.7, p < .05) in db/db Ex increased compared with the db/db CON. There were non-significant trends of mitochondrial H2O2 emission for db/db Ex in both SOL (43.07 ± 4.52 vs. 58.60 ± 2.66, p > 0.05) and GAS (33.9 ± 3.4 vs. 58.42 ± 3.7, p > .05) compared with db/db CON. The Ca2+ capacity increased in the db/db Ex at SOL muscle compared with db/db CON (1519 ± 83.3 vs. 972.8 ± 63.1, p < .05), and it only decreased in db/db CON at GAS muscle (929 ± 74.1 vs. 1518 ± 1291, p < 0.05) compared with db/+ CON. CONCLUSION: The 8-week exercise protects against T2DM-induced impairment in skeletal muscle mass, exercise capacity, and skeletal muscle mitochondrial function. Supported by the NRF-2018R1A2A3074577 and NRF-2019S1A5C2A03082727.