Brown 2008 Am J Physiol Endocrinol Metab

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Brown AE, Elstner M, Yeaman SJ, Turnbull DM, Walker M (2008) Does impaired mitochondrial function affect insulin signaling and action in cultured human skeletal muscle cells? Am J Physiol Endocrinol Metab 294:E97-102.

» PMID: 17957036 Open Access

Brown AE, Elstner M, Yeaman SJ, Turnbull DM, Walker M (2008) Am J Physiol Endocrinol Metab

Abstract: 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 microM 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 microM azide, 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. Keywords: Glucose uptake, Skeletal muscle cells, Human, Insulin

O2k-Network Lab: DE Munich Elstner M

Labels: MiParea: Respiration, mt-Medicine  Pathology: Diabetes 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Intact cells  Enzyme: Complex IV;cytochrome c oxidase  Regulation: Inhibitor 

HRR: Oxygraph-2k