ORCID
- Affourtit, Charles: 0000-0003-1776-9943
Abstract
Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells.
DOI
10.1016/j.bbabio.2013.10.012
Publication Date
2014-02-01
Publication Title
Biochim Biophys Acta
Volume
1837
Issue
2
ISSN
0006-3002
Organisational Unit
School of Biomedical Sciences
Keywords
2-deoxyglucose, 2DG, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, BSA, Cell respiratory control, DMEM, "Dulbecco's modified Eagle medium", ECAR, FCCP, FCS, Hepes, Insulin sensitivity, Mitochondrial coupling efficiency, Mitochondrial proton leak, Oxidative phosphorylation, Skeletal muscle cells, UCP, bovine serum albumin, extracellular acidification rate, fetal calf serum, trifluorocarbonylcyanide phenylhydrazone, uncoupling protein, Anaerobiosis, Animals, Cell Line, Cell Respiration, Glucose, Glycolysis, Humans, Insulin, Mitochondria, Muscle, Skeletal, Oxidative Phosphorylation, Oxygen Consumption, Palmitic Acid, Protons, Rats
First Page
270
Last Page
276
Recommended Citation
Nisr, R. B., & Affourtit, C. (2014) 'Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation.', Biochim Biophys Acta, 1837(2), pp. 270-276. Available at: https://doi.org/10.1016/j.bbabio.2013.10.012
