Short-term bed rest-induced insulin resistance cannot be explained by increased mitochondrial H2O2 emission

Mitochondrial H2O2 has been causally linked to diet-induced insulin resistance, although it remains unclear if muscle disuse similarly increases mitochondrial H2O2. Therefore, we investigated the potential that an increase in skeletal muscle mitochondrial H2O2 emission, potentially as a result of decreased ADP sensitivity, contributes to cellular redox stress and the induction of insulin resistance during short-term bed rest in 20 healthy males. Bed rest led to a decline in glucose infusion rate during a hyperinsulinaemic-euglycaemic clamp (−42 ± 2%; P < 0.001), and in permeabilized skeletal muscle fibres it decreased OXPHOS protein content (−16 ± 8%) and mitochondrial respiration across a range of ADP concentrations (−13 ± 5%). While bed rest tended to increase maximal mitochondrial H2O2 emission rates (P = 0.053), H2O2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H2O2 emission to mitochondrial O2 consumption, and markers of oxidative stress were not altered following bed rest. Altogether, while bed rest impairs mitochondrial ADP-stimulated respiration, an increase in mitochondrial H2O2 emission does not contribute to the induction of insulin resistance following short-term bed rest.