Autor:innen:
L. Mastrototaro (Düsseldorf, DE)
M. Apostolopoulou (Düsseldorf, DE)
H. Sell (Düsseldorf, DE)
S. Hartwig (Düsseldorf, DE)
D. Pesta (Düsseldorf, DE)
K. Straßburger (Düsseldorf, DE)
E. De Filippo (Düsseldorf, DE)
Y. Karusheva (Düsseldorf, DE)
S. Gancheva (Düsseldorf, DE)
D. Markgraf (Düsseldorf, DE)
S. Lehr (Düsseldorf, DE)
K. Müssig (Düsseldorf, DE)
H. Al-Hasani (Düsseldorf, DE)
J. Szendrödi (Düsseldorf, DE)
M. Roden (Düsseldorf, DE)
Introduction: Acute exercising triggers the release of small extracellular vesicles (SEV) into circulation, which might mediate tissue crosstalk. As the impact of intensive exercise training on the release of SEV is unknown, this study examined SEV number and proteomic profile in insulin sensitive (IS) and insulin resistant (IR) humans during high-intensity interval training (HIIT) in order to elucidate the role of SEV for metabolic adaptation to exercising.
Methods: Eight type 2 diabetes (T2D), 8 glucose-tolerant IR and 6 IS humans, age- and BMI-matched, performed a 12-weeks HIIT cycling protocol for 3 days/week. Before the intervention (baseline) and 72 h after the last HIIT session, whole-body insulin sensitivity was assessed with hyperinsulinemic-euglycemic clamps, protein kinase C (PKC) θ and ε activation and mitochondrial dynamics were determined in muscle biopsies by western blot and SEV were isolated from serum by size exclusion chromatography. SEV concentration was measured by Nanoparticle Tracking Analysis and proteomic profiling was done by mass spectrometry using data independent acquisition.
Results: HIIT leads to improved insulin sensitivity and increased number of SEV in T2D and IR (p< 0.05 vs baseline). Moreover, in T2D PKC activity is decreased (p< 0.05) and mitochondrial fission increased (p< 0.01). Quantitative proteomic analysis of SEV revealed a change in abundance for 258 proteins, including proteins related to glycolysis and antioxidative metabolism.
Conclusion: HIIT increases SEV number but differently affects SEV proteome in IR and IS individuals. These findings suggest a role of SEV cargo in mediating the individual response to HIIT in these individuals.