Metabolic responsiveness to training depends on insulin sensitivity and protein content of exosomes in insulin-resistant males

C E L L  B I O L O G Y

Maria Apostolopoulou, Lucia Mastrototaro, Sonja Hartwig, Dominik Pesta, Klaus Straßburger, Elisabetta de Filippo, Tomas Jelenik, Yanislava Karusheva,
Sofiya Gancheva, Daniel Markgraf, Christian Herder, K. Sreekumaran Nair,
Andreas S. Reichert , Stefan Lehr, Karsten Müssig, Hadi Al-Hasani,
Julia Szendroedi , Michael Roden

High-intensity interval training (HIIT) improves cardiorespiratory fitness (VO2max), but its impact on metabolism remains unclear. We hypothesized that 12-week HIIT increases insulin sensitivity in males with or without type 2 diabetes [T2D and NDM (nondiabetic humans)]. However, despite identically higher VO2max, mainly insulin-resistant (IR) persons (T2D and IR NDM) showed distinct alterations of circulating small extracellular vesicles (SEVs) along with lower inhibitory metabolic (protein kinase Cε activity) or inflammatory (nuclear factor κB) signaling in muscle of T2D or IR NDM, respectively. This is related to the specific alterations in SEV proteome reflecting down-regulation of the phospholipase C pathway (T2D) and up-regulated antioxidant capacity (IR NDM). Thus, SEV cargo may con-tribute to modulating the individual metabolic responsiveness to exercise training in humans.

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