Exercise and Mitochondrial Remodeling in Skeletal Muscle in Type 2 Diabetes

Abstract

Exercise is regarded as a potent stimulus in modulation of glucose utility and mitochondrial adaptations in skeletal muscle, leading to enhanced metabolic health. As mitochondria play a crucial role in sustaining metabolic homeostasis, and disturbances in mitochondrial function are highly linked with development of metabolic diseases, a comprehensive understanding of exercise-mediated mitochondrial remodeling under the pathophysiological condition of type 2 diabetes is warranted to develop an efficient therapeutic strategy. Although it is evident that the primary etiology of type 2 diabetes is insulin resistance, there is accumulating evidence linking abnormal mitochondrial functional and morphological properties to development of type 2 diabetes. Despite this, the precise molecular and cellular events that underline these phenomena remain uncertain. Mitochondria are highly dynamic subcellular organelles that can change mass and shape as necessary via coordinated processes such as mitochondrial fusion, fission, and biogenesis. Mitochondrial fusion is controlled by proteins, including mitofusin-1, mitofusin-2, and optic atrophy protein 1, while the fission process is mainly modulated by control of fission protein 1 and dynamin-related protein 1. Peroxisome proliferator-activated receptor gamma coactivator-1α acts as a master controller of mitochondrial biogenesis. The present review’s primary aims were to briefly discuss the cellular mechanisms of muscle fiber type-dependent glucose uptake and to highlight emerging evidence linking disturbances in mitochondrial dynamics to development of insulin resistance and type 2 diabetes. The potential for exercise to normalize type 2 diabetes-induced aberrant mitochondrial integrity is also addressed.