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Lookup NU author(s): Dr Audrey Brown, Dr Matthias Elstner, Emeritus Professor Steve Yeaman, Emeritus Professor Doug Turnbull, Professor Mark Walker
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Insulin-resistant type 2 diabetic patients have been reported to have impaired skeletal muscle mitochondrial respiratory function. A key question is whether decreased mitochondrial respiration contributes directly to the decreased insulin action. To address this, a model of impaired cellular respiratory function was established by incubating human skeletal muscle cell cultures with the mitochondrial inhibitor sodium azide and examining the effects on insulin action. Incubation of human skeletal muscle cells with 50 and 75 μM azide resulted in 48 ± 3% and 56 ± 1% decreases, respectively, in respiration compared with untreated cells mimicking the level of impairment seen in type 2 diabetes. Under conditions of decreased respiratory chain function, insulin-independent (basal) glucose uptake was significantly increased. Basal glucose uptake was 325 ± 39 pmol/min/mg (mean ± SE) in untreated cells. This increased to 669 ± 69 and 823 ± 83 pmol/min/mg in cells treated with 50 and 75 μMazide, respectively (vs. untreated, both P < 0.0001). Azide treatment was also accompanied by an increase in basal glycogen synthesis and phosphorylation of AMP-activated protein kinase. However, there was no decrease in glucose uptake following insulin exposure, and insulin-stimulated phosphorylation of Akt was normal under these conditions. GLUT1 mRNA expression remained unchanged, whereas GLUT4 mRNA expression increased following azide treatment. In conclusion, under conditions of impaired mitochondrial respiration there was no evidence of impaired insulin signaling or glucose uptake following insulin exposure in this model system. Copyright © 2008 the American Physiological Society.
Author(s): Brown AE, Elstner M, Yeaman SJ, Turnbull DM, Walker M
Publication type: Article
Publication status: Published
Journal: American Journal of Physiology - Endocrinology and Metabolism
Year: 2008
Volume: 294
Issue: 1
Pages: E97-E102
ISSN (print): 0193-1849
ISSN (electronic): 1522-1555
Publisher: American Physiological Society
URL: http://dx.doi.org/10.1152/ajpendo.00267.2007
DOI: 10.1152/ajpendo.00267.2007
PubMed id: 17957036
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