We determined if bed rest increased mitochondrially derived reactive oxygen species and cellular redox stress, contributing to the induction of insulin resistance. Bed rest decreased maximal and submaximal ADP-stimulated mitochondrial respiration. Bed rest did not alter mitochondrial H2O2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H2O2 emission to mitochondrial O-2 consumption or markers of oxidative stress The present data suggest strongly that mitochondrial H2O2 does not contribute to bed rest-induced insulin resistance 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 O-2 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.
- bed rest
- insulin resistance
- muscle disuse
- reactive oxygen species
- ADENINE-NUCLEOTIDE TRANSLOCASE