THE EFFECTS OF AEROBIC EXERCISE ON SKELETAL MUSCLE METABOLISM, MORPHOLOGY AND IN SITU ENDURANCE IN DIABETIC RATS

The effects of aerobic exercise training on skeletal muscle endurance capacity were examined in diabetic rats in situ. Moderate diabetes was induced by iv injection of streptozotocin and an exercise training program on a treadmill was carried out for 8 weeks. The animals randomly assigned to one of the four experimental groups: control-sedentary (CS), control-exercise (CE), diabetic-sedentary (DS) or diabetic-exercise (DE). The changes in the muscle endurance capacity were evaluated through the square wave impulses (supramaximal) of 0.2-ms duration at 1 Hz in the in situ gastrocnemius-soleus muscle complex. Muscle was stimulated continuously until tension development reduced to the half of this maximal value. Time interval between the beginning and the end of stimulation period is defined as contraction duration. Following the training period, blood glucose level reduced significantly in the DE group compared to DS group (p < 0.05). The soles muscle citrate synthase activity was increased significantly in both of the trained groups compared to sedentary animals (p < 0.05). Fatigued muscle lactate values were not significantly different from each other. Ultrastractural abnormality of the skeletal muscle in DS group disappeared with training. Presence of increased lipid droplets, mitochondria clusters and glycogen accumulation was observed in the skeletal muscle of DE group. The contraction duration was longer in the DE group than others (p < 0.001). Fatigue resistance of exercised diabetic animals may be explained by increased intramyocellular lipid droplets, high blood glucose level and muscle citrate synthase activity. Key Points Aerobic training of diabetic animals increased the endurance capacity. Presence of abnormal ultrastructural alterations with diabetes disaapered with regular training. Increased intramyocelluler lipid droplets, high blood glucose level with citrate synthase activity may explain this finding. Key Words: Training, citrate synthase, muscle endurance, ultrastructure, diabetes Introduction Diabetes mellitus (DM), is a catabolic disease which mainly affects the skeletal muscle, adipose tissue and liver by bringing about impairments in carbohydrate and lipid metabolism. Fat and carbohydrate are the principal substrates that fuel aerobic ATP synthesis in skeletal muscle (Van Loon, 2004). Elevated plasma concentration of those substrates in DM causes serious damages in ultrastructure and metabolism of the skeletal muscle together with other tissues. Reduction of muscle weight with abnormal arrangement of myofibrils, mitochondrial swelling and lysis of mitochondrial cristae at spontaneous diabetic rats are reported previously as the ultrastructural abnormalities (Ozaki et al., 2001). Metabolic changes classified as altered ratio between glycolytic and oxidative enzyme activities of skeletal muscle that suggests the irregularity between mitochondrial oxidative capacity and capacity of glycolysis (Simoneau and Kelley, 1997). On the other hand there has been a long standing interest with the relationship between muscle lipid content and skeletal muscle insulin resistance. Various studies have reported a strong association between intramyocellular lipid accumulation, and development of DM (Jacob et al., 1999; Koyama et al., 1997; Oakes et al., 1997; Perseghin et al., 2002). Adaptability to exercise is an enormous property of the skeletal muscle. The high capacity to modulate energy production rate, blood flow and substrate utilization indicate the metabolic flexibility of this tissue (Saltin and Gollnick, 1983). Due to attenuating effect on skeletal muscle catabolism, aerobic exercise training is frequently suggested for prevention and treatment of DM. Response to aerobic exercise is compromised with an adaptive increase in insulin responsiveness and sensitivity (Mikines et al., 1989; Nesher et al., 1985) and enhanced glucose uptake (Hayashi et al., 1997; Rodnick et al., 1992) in skeletal muscle. Previous studies had shown that increased GLUT4 protein is a component of the adaptive response of muscle to endurance training and associated with increased capacity for glucose transport into the skeletal muscle (Rodnick et al., 1992). Exercise can also increase glucose uptake in skeletal muscle by increasing both insulin activity (Nesher et al., 1985; Mikines et al., 1989) and membrane GLUT4 exposition (Goodyear et al., 1992; Reynolds et al., 1997). Nobre and Ianuzzo (1985) had shown that enzymatic potential of all skeletal muscle types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin. In addition to that, the importance of muscle contraction and insulin for fatty acid transporter (FAT-CD36) translocation from an intracellular depot to the plasma membrane had been shown previously (Dyck and Bonen, 1998; Dyck et al., 2000; 2001; Bonen et al., 2000; Luiken et al., 2002). As a result of these consecutive changes, regular aerobic training may enhance the endurance of muscle by increasing the availability of energy substrates for skeletal muscle contraction together with oxidation of glucose and fatty acids (Bonen et al., 1999). Changes in the enzymatic activity as well as the membrane transport protein content may explain the beneficial effect of regular training in DM. On the other hand, there is an uncertainty about the effect of regular exercise on skeletal muscle endurance capacity in diabetic animals. Although endogenous fat stores correspond to a tremendous energy store and especially in trained subjects, utilization of intramyocellular triacylglycerol may account for considerable portion of energy requirement (Van Loon, 2004) during aerobic exercise. Therefore, in terms of endurance capacity, elevated plasma glucose level together with increased intramyocellular triacylglycerol may be an advantage for diabetic animals compared to controls. With this in mind, we aimed to investigate detailed effects of regular exercise on the endurance capacity of the isolated skeletal muscle in situ.