Short-term bed rest-induced insulin resistance cannot be explained by increased mitochondrial H2 O2 emission

Marlou L Dirks, Paula M Miotto, Gijs H Goossens, Joan M Senden, Heather L Petrick, Janneau van Kranenburg, Luc J C van Loon, Graham P Holloway, Marlou L Dirks, Paula M Miotto, Gijs H Goossens, Joan M Senden, Heather L Petrick, Janneau van Kranenburg, Luc J C van Loon, Graham P Holloway

Abstract

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 H2 O2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H2 O2 emission to mitochondrial O2 consumption or markers of oxidative stress The present data suggest strongly that mitochondrial H2 O2 does not contribute to bed rest-induced insulin resistance ABSTRACT: Mitochondrial H2 O2 has been causally linked to diet-induced insulin resistance, although it remains unclear if muscle disuse similarly increases mitochondrial H2 O2 . Therefore, we investigated the potential that an increase in skeletal muscle mitochondrial H2 O2 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 H2 O2 emission rates (P = 0.053), H2 O2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H2 O2 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 H2 O2 emission does not contribute to the induction of insulin resistance following short-term bed rest.

Trial registration: ClinicalTrials.gov NCT02521025.

Keywords: bed rest; insulin resistance; mitochondria; muscle disuse; reactive oxygen species.

© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.

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