The effects of extracellular vesicles and their cargo on metabolism and its adaptation to physical exercise in insulin resistance and type 2 diabetes

Lifestyle modification represents the first-line strategy for the prevention and treatment of type 2 diabetes mellitus (T2DM), which is frequently associated with obesity and characterized by defective pancreatic insulin secretion and/or insulin resistance. Exercise training is an essential component of lifestyle modification and has been shown to ameliorate insulin resistance by reducing body fat mass and by enhancing skeletal muscle mitochondrial biogenesis and insulin-independent glucose uptake. Additionally, exercising stimulates the release of exerkines such as metabolites or cytokines, but also long non-coding RNA, microRNAs, cell-free DNA (cf-DNA), and extracellular vesicles (EVs), which contribute to inter-tissue communication. There is emerging evidence that EV number and content are altered in obesity and T2DM and may be involved in several metabolic processes, specifically either worsening or improving insulin resistance. This review summarizes the current knowledge on the metabolic effects of exercise training and on the potential role of humoral factors and EV as new biomarkers for early diagnosis and tailored treatment of T2DM.

Automated summary

Lifestyle modification is the first-line approach for preventing and treating type 2 diabetes mellitus (T2DM), which is often linked to obesity and characterized by insulin resistance and defective pancreatic insulin secretion. Exercise training plays a crucial role in lifestyle modification by reducing body fat mass, enhancing skeletal muscle mitochondrial biogenesis and insulin-independent glucose uptake to improve insulin resistance. Furthermore, exercise stimulates the release of various factors such as exerkines, long non-coding RNA, microRNAs, cell-free DNA, and extracellular vesicles, which contribute to inter-tissue communication. The altered number and content of extracellular vesicles in obesity and T2DM may be involved in metabolic processes related to insulin resistance, suggesting their potential as new biomarkers for early diagnosis and personalized treatment of T2DM.