Beneficial effects of exercise on muscle mitochondrial function in diabetes mellitus

The physiopathology of diabetes mellitus has been closely associated with a variety of alterations in mitochondrial histology, biochemistry and function. Generally, the alterations comprise increased mitochondrial reactive oxygen and nitrogen species (RONS) generation, resulting in oxidative stress and damage; decreased capacity to metabolize lipids, leading to intramyocyte lipid accumulation; and diminished mitochondrial density and reduced levels of uncoupling proteins (UCPs), with consequent impairment in mitochondrial function. Chronic physical exercise is a physiological stimulus able to induce mitochondrial adaptations that can counteract the adverse effects of diabetes on muscle mitochondria. However, the mechanisms responsible for mitochondrial adaptations in the muscles of diabetic patients are still unclear. The main mechanisms by which exercise may be considered an important non-pharmacological strategy for preventing and/or attenuating diabetes-induced mitochondrial impairments may involve (i) increased mitochondrial biogenesis, which is dependent on the increased expression of some important proteins, such as the 'master switch' peroxisome proliferator-activated receptor (PPAR)-gamma-coactivator-1alpha (PGC-1alpha) and heat shock proteins (HSPs), both of which are severely downregulated in the muscles of diabetic patients; and (ii) the restoration or attenuation of the low UCP3 expression in skeletal muscle mitochondria of diabetic patients, which is suggested to play a pivotal role in mitochondrial dysfunction.There is evidence that chronic exercise and lifestyle interventions reverse impairments in mitochondrial density and size, in the activity of respiratory chain complexes and in cardiolipin content; however, the mechanisms by which chronic exercise alters mitochondrial respiratory parameters, mitochondrial antioxidant systems and other specific proteins involved in mitochondrial metabolism in the muscles of diabetic patients remain to be elucidated.