Exercise-mediated Rescue of Mitochondrial Dysfunctions Driving Insulin Resistance

The overarching aim of this intervention study is to interrogate the interconnection between the muscle mitochondrial adaptations and the changes in muscle insulin sensitivity elicited by exercise training in individuals harbouring pathogenic mitochondrial DNA mutations associated with an insulin-resistant phenotype. In a within-subject parallel-group longitudinal design, participants will undergo an exercise training intervention with one leg, while the contralateral leg will serve as an inactive control. After the exercise intervention, patients will attend an experimental trial including: * A hyperinsulinemic-euglycemic clamp combined with measurements of femoral artery blood flow and arteriovenous difference of glucose * Muscle biopsy samples