Does impaired mitochondrial function affect insulin signaling and action in cultured human skeletal muscle cells?
Open accessAbstract
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 μM 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.
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Treatment of muscle cells with azide increased basal glucose uptake without affecting insulin-stimulated glucose uptake in myotubes.
“treatment of the muscle cells with azide, an inhibitor of mitochondrial complex IV, increased basal glucose uptake without affecting insulin-stimulated glucose uptake in myotubes [136].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [136]
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Pathogenesis of insulin resistance in skeletal muscle
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- Authors
- Brown, A. E., Elstner, M., Yeaman, S. J., Turnbull, D. M., & Walker, M.
- Affiliations
- Newcastle University (GB)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2008-01
- Volume
- 294
- Issue
- 1
- Pages
- E97-E102
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2162803859
- Cited by
- 8
- References
- 30
- Citations by year
- 2018: 1 · 2017: 2 · 2012: 2
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust (074454)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitochondrial dysfunction, insulin resistance, type 2 diabetes, skeletal muscle, insulin signaling, glucose uptake, mitochondrial respiration, sodium azide, AMPK, Akt phosphorylation, GLUT4, glycogen synthesis, insulin-independent glucose uptake
- MeSH terms
- Cells, Cultured, Electron Transport Complex IV, Diabetes Mellitus, Type 2, Electron Transport, Enzyme Inhibitors, Glucose, Glycogen, Humans, Insulin, Mitochondria, Multienzyme Complexes, Phosphorylation, RNA, Messenger, Signal Transduction, Protein Serine-Threonine Kinases, Muscle, Skeletal, Muscle Fibers, Skeletal, Sodium Azide, Proto-Oncogene Proteins c-akt, Glucose Transporter Type 1, Glucose Transporter Type 4, AMP-Activated Protein Kinases
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