Type 2 Diabetes mellitus (T2DM) is a chronic disease that affects approximately 90-95% of diabetics and has grown considerably in recent years. The cause of T2DM is a combination of a resistance to insulin action as well as compensatory responses of hormone secretion. This combination results in alterations in the metabolism of carbohydrates, lipids, and proteins due to a deficient action of insulin in peripheral target tissues, which have a decreased response at one or more points of the hormone signaling pathway[4, 5]. The risk of developing type 2 diabetes increases with age, obesity, and physical inactivity, all of which contribute to a metabolism imbalance, principally in lipid profiles. The present study aimed to compare the effects of continuous, intermittent, and strength training on serum and tissue variables on the lipid metabolism of alloxan rats.
The present study data showed an efficacy of neonatal alloxan administration, proved by the changes in insulin sensitivity in alloxan animals when assessing the serum glucose disappearance rate in ITT after 28 days of age. These findings are consistent with previous studies conducted using a neonatal alloxan model[12, 33, 34], which showed lower insulin sensitivity in alloxan animals.
Chronic physical training has an important role in improving insulin sensitivity[35, 36] and the lipid profile in T2DM, but the optimal level of effort that should be applied remains unknown. The present study used three physical training protocols with different intensities of effort to evaluate the effects of aerobic and anaerobic capacity on alloxan animals.
Assessments of aerobic capacity are performed using procedures that investigate a transition zone during exercise to ascertain where there is a predominance of aerobic metabolism over anaerobic metabolism in the supply of adenosine triphosphate to muscle activity. The procedures utilize an analysis of blood lactate concentration as a metabolic parameter because it is a reliable measure of the transition for characterizing the chronic effects of training as well as the effort involved. In the present study, a stress test was conducted to measure lactacidemia in animals after 12 weeks of continuous, intermittent, and strength swimming.
No differences were found in lactate kinetics among the groups that underwent the continuous training protocol. These findings are consistent with Ribeiro et al., who conducted a study using a neonatal alloxan model that demonstrated similar lactacidemia among groups. The response of sedentary animals to the test could be interpreted as moderate intensity with a predominance of aerobic metabolism, given the values of lactate that were achieved and the moderate intensity at the start of the training program. For the intermittent training protocol, although there was the same total weekly load as in the continuous training protocol, a lower lactate disappearance rate in sedentary animals was found, which showed that training had an effect. By measuring the lactate kinetics related to strength training, a higher degree of lactacidemia in sedentary animals compared to controls was found throughout the test, which demonstrates the positive effect of the applied training. These results confirm the chronic effect of exercise in addition to demonstrating a positive response of alloxan animals to different protocols and intensities of effort.
Due to the relationship between changes in insulin sensitivity and lipid metabolism in T2DM and the role of physical exercise, the present study also assessed the animals lipid profile.
High levels of circulating FFAs are correlated with lower phosphorylation and insulin activation (IRS/PI3q). The presence of FFAs provides a direct relationship with insulin resistance that may result from the accumulation of triglycerides in muscle and liver. Furthermore, the increase of these metabolites due to the oxidation of fat in muscle is capable activating protein kinase C (PKC) and inducing serine phosphorylation of the insulin receptor (IR) and its substrates, which are important mechanisms that explain the relationship between the accumulation of fat tissue and resistance to insulin[39, 40]. The present study thus assessed the serum concentrations of FFAs, triglycerides, total cholesterol, and total lipids in addition to lipid levels in adipose tissue, the gastrocnemius muscle, the liver, and the heart.
The serum concentration of FFAs showed a higher concentration in sedentary alloxan animals, but a reduction in the level was found after continuous and intermittent swim training. Additionally, intermittent and strength training were more effective in reducing the level of fatty acids in alloxan animals than in controls. Oliveira et al. found similar results in a neonatal alloxan model. Alloxan animals showed higher levels of FFAs that diminished after continuous swimming. Stolen et al. found results in db/db animals that were similar to the FFA concentrations after 13 weeks of intermittent training. Ghelfi et al. found no differences in the concentrations of FFAs in type 1 diabetic subjects after intermittent training of high and moderate intensity. Similar results were found in the serum concentrations of FFAs in alloxan-induced diabetic adult animals. Holten et al. found similar results in a study of type 2 diabetic subjects after strength training. Thus, it is noted that the training protocols applied in the current study were effective in reducing the accumulation of serum FFAs in the animals. Therefore, they likely play an important role in the prevention and treatment of metabolic disturbances in lipid metabolism that are caused by insulin resistance in T2DM. No change was observed between the groups in the concentration of triglycerides. This result differs from the study of alloxan adult animals, which reported the animals having lower concentrations of triglycerides after 7 days of training on a treadmill. In the present study, strength training was more effective in reducing total cholesterol levels in alloxan animals, and strength and continuous training were better for the maintenance of total serum lipids. In an experimental model of alloxan-induced diabetes in adult animals, Moura et al. found no significant differences in serum cholesterol levels even after 44 days of continuous training at moderate swimming intensity. In a study using Zucker Diabetic Fatty (ZDF) rats as a T2DM model, diabetic animals had reduced serum cholesterol levels after 12 weeks of swim training at moderate intensity, suggesting the importance of physical training on the lipid profile of T2DM.
Many individuals with T2DM are overweight or obese. Thus, their distribution and accumulation of lipids in adipose tissue differ. Therefore, analyses of lipid levels in the adipose tissue in the retroperitoneal, mesenteric, and subcutaneous regions of rats were performed, although no differences were found in the concentrations of these lipids.
Obesity and alterations in the lipids metabolism has been shown as a cause of insulin resistance[46, 47]. In recent years studies have shown a relationship between organ dysfunction and lipids storage in tissues such as liver, heart, pancreas, and skeletal muscle. It is known that exercise training can reduce the changes in lipid metabolism of high-risk subjects for development of T2DM.
Therefore, the present study also evaluated total lipid levels in the gastrocnemius muscle, liver, and heart. Differences were noted only in liver tissue for alloxan animals that underwent continuous training, which showed lower concentrations. These results corroborate with those of Oliveira et al. who, using the same neonatal alloxan model, reported a higher use of lipids in the liver after physical training, thereby reducing the amount in the tissue. Moura et al. found similar data in a type 1 diabetes experimental model, which highlights the importance of exercise in the control of total lipids in liver tissue.
In summary, physical training at different intensities of effort and on different schedules was key in the reduction of lipid levels and control of changes in lipid metabolism in alloxan animals. It may therefore be concluded that both high and moderate intensity training were effective in improving the lipid profile of alloxan animals. Therefore, exercise can play an important role in the prevention and treatment of metabolic alterations in lipid metabolism that are caused by insulin resistance T2DM.