Effects of acute hyperinsulinemia on skeletal muscle mitochondrial function, reactive oxygen species production, and metabolism in premenopausal women.
Citation | Warren, Jonathan L, et al. “Effects of Acute Hyperinsulinemia on Skeletal Muscle Mitochondrial Function, Reactive Oxygen Species Production, and Metabolism in Premenopausal Women”. 2017. Metabolism: Clinical and Experimental, vol. 77, 2017, pp. 1–12. |
Center | University of Alabama at Birmingham |
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Author | Jonathan L Warren, Sule Bulur, Fernando Ovalle, Samuel T Windham, Barbara A Gower, Gordon Fisher |
Keywords | Hyperinsulinemia, Mitochondrial plasticity, Mitochondrial uncoupling, Respirometry |
Abstract |
BACKGROUND: Acute metabolic demands that promote excessive and/or prolonged reactive oxygen species production may stimulate changes in mitochondrial oxidative capacity. PURPOSE: To assess changes in skeletal muscle HO production, mitochondrial function, and expression of genes at the mRNA and protein levels regulating energy metabolism and mitochondrial dynamics following a hyperinsulinemic-euglycemic clamp in a cohort of 11 healthy premenopausal women. METHODS: Skeletal muscle biopsies of the vastus lateralis were taken at baseline and immediately following the conclusion of a hyperinsulinemic-euglycemic clamp. Mitochondrial production of HO was quantified fluorometrically and mitochondrial oxidation supported by pyruvate, malate, and succinate (PMS) or palmitoyl carnitine and malate (PCM) was measured by high-resolution respirometry in permeabilized muscle fiber bundles. mRNA and protein levels were assessed by real time PCR and Western blotting. RESULTS: HO emission increased following the clamp (P<0.05). Coupled respiration (State 3) supported by PMS and the respiratory control ratio (index of mitochondrial coupling) for both PMS and PCM were lower following the clamp (P<0.05). IRS1 mRNA decreased, whereas PGC1α and GLUT4 mRNA increased following the clamp (P≤0.05). PGC1α, IRS1, and phosphorylated AKT protein levels were higher after the clamp compared to baseline (P<0.05). CONCLUSIONS: This study demonstrated that acute hyperinsulinemia induced HO production and a concurrent decrease in coupling of mitochondrial respiration with ATP production in a cohort of healthy premenopausal women. Future studies should determine if this uncoupling ameliorates peripheral oxidative damage, and if this mechanism is impaired in diseases associated with chronic oxidative stress. |
Year of Publication |
2017
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Journal |
Metabolism: clinical and experimental
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Volume |
77
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Number of Pages |
1-12
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Date Published |
12/2017
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ISSN Number |
1532-8600
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DOI |
10.1016/j.metabol.2017.08.004
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Alternate Journal |
Metab. Clin. Exp.
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PMID |
29132536
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PMCID |
PMC5726454
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