Reductions in mitochondrial function have been proposed to cause insulin resistance, however the possibility that impairments in insulin signaling negatively affects mitochondrial bioenergetics has received little attention. Therefore, we tested the hypothesis that insulin could rapidly improve mitochondrial ADP sensitivity, a key process linked to oxidative phosphorylation and redox balance, and if this phenomenon would be lost following high-fat diet (HFD)-induced insulin resistance. Insulin acutely (60 min post I.P.) increased submaximal (100–1000 µM ADP) mitochondrial respiration ∼2-fold without altering maximal (>1000 µM ADP) respiration, suggesting insulin rapidly improves mitochondrial bioenergetics. The consumption of HFD impaired submaximal ADP-supported respiration ∼50%, however, despite the induction of insulin resistance, the ability of acute insulin to stimulate ADP sensitivity and increase submaximal respiration persisted. While these data suggest that insulin mitigates HFD-induced impairments in mitochondrial bioenergetics, the presence of a high intracellular lipid environment reflective of an HFD (i.e. presence of palmitoyl-CoA) completely prevented the beneficial effects of insulin. Altogether, these data show that while insulin rapidly stimulates mitochondrial bioenergetics through an improvement in ADP sensitivity, this phenomenon is possibly lost following HFD due to the presence of intracellular lipids.
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Cover Image
SMCHD1 is an epigenetic regulator that mediates gene expression silencing at targeted sites across the genome. In this issue Gurzau and colleagues (pp. 2555–2569) use biophysical techniques to we demonstrate that the SMCHD1 ATPase undergoes dimerization in a process that is dependent on both the N-terminal Ubiquitin-like domain and ATP binding. The cover image shows immunofluorescence with DAPI staining in cyan and SMCHD1 showing in yellow. Scale bars are 20 µm. Image provided by James M. Murphy.
Insulin rapidly increases skeletal muscle mitochondrial ADP sensitivity in the absence of a high lipid environment
Henver S. Brunetta, Heather L. Petrick, Bayley Vachon, Everson A. Nunes, Graham P. Holloway; Insulin rapidly increases skeletal muscle mitochondrial ADP sensitivity in the absence of a high lipid environment. Biochem J 16 July 2021; 478 (13): 2539–2553. doi: https://doi.org/10.1042/BCJ20210264
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