Skeletal muscle
insulin resistance and
mitochondrial dysfunction are some of the major pathological defects implicated in the development of
type 2 diabetes (T2D). Therefore, it has become necessary to understand how common interventions such as physical exercise and
caloric restriction affect metabolic function, including physiological processes that implicate skeletal muscle dysfunction within a state of T2D. This review critically discusses evidence on the impact of physical exercise and
caloric restriction on markers of
insulin resistance and
mitochondrial dysfunction within the skeletal muscle of patients with T2D or related metabolic complications. Importantly, relevant information from clinical studies was acquired through a systematic approach targeting major electronic databases and search engines such as PubMed, Google Scholar, and Cochrane library. The reported evidence suggests that interventions like physical exercise and
caloric restriction, within a duration of approximately 2 to 4 months, can improve
insulin sensitivity, in part by targeting the
phosphoinositide 3-kinases/
protein kinase B pathway in patients with T2D. Furthermore, both physical exercise and
caloric restriction can effectively modulate markers related to improved mitochondrial function and dynamics. This was consistent with an improved modulation of mitochondrial oxidative capacity and reduced production of
reactive oxygen species in patients with T2D or related metabolic complications. However, such conclusions are based on limited evidence, additional clinical trials are required to better understand these interventions on pathological mechanisms of T2D and related abnormalities.