title: Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation.
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.
authors.affiliation: School of Biomedical & Healthcare Sciences, Plymouth University, Drake Circus, Plymouth, UK. Electronic address: raid.nisr@plymouth.ac.uk.
authors.forename: Raid B
authors.initials: RB
authors.lastname: Nisr
authors.affiliation: School of Biomedical & Healthcare Sciences, Plymouth University, Drake Circus, Plymouth, UK. Electronic address: charles.affourtit@plymouth.ac.uk.
authors.forename: Charles
authors.initials: C
authors.lastname: Affourtit
mesh_terms: D000693:Anaerobiosis / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology; D011522:Protons; D051381:Rats
chemical_list: D007328:Insulin; D011522:Protons; D019308:Palmitic Acid; D005947:Glucose
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