Impaired mitochondrial oxidative phosphorylation and supercomplex assembly in rectus abdominis muscle of diabetic obese individuals
Open accessAbstract
Aims/hypothesis Skeletal muscle mitochondrial dysfunction has been documented in patients with type 2 diabetes mellitus; however, specific respiratory defects and their mechanisms are poorly understood. The aim of the current study was to examine oxidative phosphorylation and electron transport chain (ETC) supercomplex assembly in rectus abdominis muscles of 10 obese diabetic and 10 obese non-diabetic individuals.Methods Twenty obese women undergoing Roux-en-Y gastric bypass surgery were recruited for this study. Muscle samples were obtained intraoperatively and subdivided for multiple analyses, including high-resolution respirometry and assessment of supercomplex assembly. Clinical data obtained from referring physicians were correlated with laboratory findings.Results Participants in both groups were of a similar age, weight and BMI. Mitochondrial respiration rates were markedly reduced in diabetic vs non-diabetic patients. This defect was observed during maximal ADP-stimulated respiration in the presence of complex I-linked substrates and complex I- and II-linked substrates, and during maximal uncoupled respiration. There were no differences in fatty acid (octanoyl carnitine) supported respiration, leak respiration or isolated activity of cytochrome c oxidase. Intriguingly, significant correlations were found between glycated haemoglobin (HbA1c) levels and maximal respiration or respiration supported by complex I, complex I and II or fatty acid. In the muscle of diabetic patients, blue native gel electrophoresis revealed a striking decrease in complex I, III and IV containing ETC supercomplexes.Conclusions/interpretation These findings support the hypothesis that ETC supercomplex assembly may be an important underlying mechanism of muscle mitochondrial dysfunction in type 2 diabetes mellitus.
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A decrease in mitochondrial respiration supported by complex I and complex II substrates or octanoyl carnitine significantly correlates with glycated haemoglobin.
“Most importantly, a decrease in mitochondrial respiration supported by complex I and complex II substrates or octanoyl carnitine significantly correlated with glycated haemoglobin (Antoun et al., 2015).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Antoun et al., 2015
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- Authors
- Antoun, G., McMurray, F., Thrush, A. B., Patten, D. A., Peixoto, A. C., Slack, R. S., McPherson, R., Dent, R., & Harper, M.-E.
- Affiliations
- University of Ottawa (CA)
- Ottawa Heart Institute (CA)
- Ottawa Hospital (CA)
- Corresponding author
- Harper, Mary-Ellen
- Venue
- Diabetologia
- Published
- 2015-09-24
- Volume
- 58
- Issue
- 12
- Pages
- 2861-2866
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W1414125020
- Cited by
- 112
- References
- 11
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 12 · 2023: 9 · 2022: 14 · 2021: 16 · 2020: 13 · 2019: 16 · 2018: 10 · 2017: 7 · 2016: 8
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-11-26)
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- University of Ottawa
- Canadian Institutes of Health Research (MOP57810, MOP136936)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- type 2 diabetes, obesity, oxidative phosphorylation, rectus abdominis, mitochondrial respiration, complex I, HbA1c, Roux-en-Y gastric bypass
- MeSH terms
- Adenosine Diphosphate, Adult, Electron Transport Complex IV, Diabetes Mellitus, Type 2, Fatty Acids, Female, Glycated Hemoglobin, Humans, Mitochondria, Obesity, Oxidative Phosphorylation, Rectus Abdominis, Muscle, Skeletal, Electron Transport Complex I, Electron Transport Chain Complex Proteins
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