Specific cardiorespiratory and metabolic improvements are sustained after exercise training cessation in males with type 2 diabetes

High-intensity interval training (HIIT) generally improves cardiorespiratory fitness (VO2max), while it increases insulin sensitivity and secretion of small extracellular vesicles (sEV) mainly in insulin resistant individuals without and with type 2 diabetes (T2D). However, it is unknown whether the HIIT-induced metabolic benefits are similarly sustained across people with different degree of glucose tolerance at 4 weeks after stopping the HIIT intervention.

Age- and BMI-matched humans with (T2D: n=20) and without T2D (insulin resistant, IR: n=10; insulin sensitive, IS: n=12) underwent hyperinsulinemic-euglycemic clamps, spiroergometry, ectopic lipid quantification and muscle biopsies after 12-week HIIT and after subsequent 4-week detraining. Additionally, sEV were isolated from serum by size exclusion chromatography and characterized by nanoparticle tracking analysis (NTA), electron microscopy (EM), western blot (WB) and mass spectrometry (MS).

Whole-body (mainly muscle) insulin sensitivity (M-value) significantly differed between T2D, IR and IS before intervention (3.0±0.4, 4.2±0.4, 7.4±0.4 mg*kg-1*min-1) and between T2D and IS after HIIT (4.3±0.6, 7.2±0.6 mg*kg-1*min-1). After detraining, VO2max declined by 7% in T2D (p< 0.001) and IR (p< 0.05), whereas M-value decreased by 28% and returned to baseline values only in T2D (p< 0.001). Hepatic insulin sensitivity and lipid content remained unchanged in all groups. Of note, T2D and IR after detraining exhibited a persistent increase (p< 0.01 and p< 0.05 vs baseline, respectively) in the number of circulating sEV, with a mean diameter<200 nm, as assessed by NTA and EM. WB confirmed the presence of EV markers and the absence of serum contaminants. Proteomic data identified 1114 proteins in the isolated sEV and the gene ontology cellular component enrichment analysis showed an overrepresentation of proteins associated with EV. Finally, differential abundance analysis revealed 186 differentially abundant proteins across the distinct groups after detraining, with an upregulation of proteins associated with inflammation (MPO, ANXA1, ANXA3, ITGB2) and oxidative stress (GPX3, PRDX1/2) in sEV isolated from T2D and IR in comparison to sEV derived from IS.

In conclusion, HIIT-induced release of sEV and their protein cargo likely contribute to the differences in the sustainability of cardiorespiratory and metabolic improvements observed after detraining in individuals with and without T2D, indicating a role of sEV in mediating exercise-induced inter-organ crosstalk.

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Artikel online veröffentlicht:
18. April 2024