Mitochondrial reactive oxygen species generation in obese non-diabetic and type 2 diabetic participants
Open accessAbstract
Aims/hypothesis The aim of this study was to measure mitochondrial reactive oxygen species (ROS) production directly from skeletal muscle biopsies obtained from obese insulin-resistant non-diabetic and type 2 diabetic participants. Methods Ten lean healthy, ten obese non-diabetic and ten type 2 diabetic participants received a euglycaemic-hyperinsulinaemic clamp to measure whole body insulin sensitivity. Mitochondria were isolated from skeletal muscle biopsies, and mitochondrial ATP synthesis and hydrogen peroxide production were measured ex vivo under conditions that maximally stimulate ATP synthesis and ROS production using chemiluminescent and fluorescent techniques, respectively. Results Compared with lean controls, both obese non-diabetic and type 2 diabetic participants were resistant to insulin, and had a reduced rate of mitochondrial ATP production. Obese insulin-resistant participants had a decreased rate of mitochondrial ROS production, while ROS production rate in participants with type 2 diabetes was similar to that in lean healthy participants. In non-diabetic participants, the rate of ROS production was strongly correlated with the rate of ATP synthesis and the glucose disposal rate measured with the euglycaemic-hyperinsulinaemic clamp. The ROS/ATP ratio in obese insulin-resistant participants was similar to that in lean insulin-sensitive participants, while the ratio was significantly elevated in type 2 diabetes participants. Conclusions/interpretation Since, in absolute terms, the maximal capacity for mitochondrial ROS production was not increased in either obese insulin-resistant participants or in type 2 diabetic participants, these results do not favour a role for increased mitochondrial ROS production in the pathogenesis of insulin resistance in human skeletal muscle. However, care should be taken in extrapolating these ex vivo observations to the in vivo situation.
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Lower rates of ROS production in obese individuals, but not type 2 diabetic individuals, have been reported.
“Lower rates of ROS production in obese individuals, but not type 2 diabetic individuals, have been reported (37).”
The study reporting lower ROS production did not report maximal ROS production rates because mitochondria were not incubated with oligomycin during measurements.
“However, this study did not report maximal ROS production rates because mitochondria were not incubated with oligomycin during the measurements.”
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- Authors
- Abdul-Ghani, M. A., Jani, R., Chavez, A., Molina-Carrion, M., Tripathy, D., & DeFronzo, R. A.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- ORCID
- Tripathy, D.
- Venue
- Diabetologia
- Published
- 2009-01-30
- Volume
- 52
- Issue
- 4
- Pages
- 574-582
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2071572735
- Cited by
- 83
- References
- 36
- Citations by year
- 2024: 4 · 2023: 6 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 7 · 2012: 8
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- National Institutes of Health
- U.S. Public Health Service (24092)
- National Center for Research Resources (M01RR001346, RR-01346)
- 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
- mitochondrial reactive oxygen species, hydrogen peroxide production, type 2 diabetes, obesity, insulin resistance, skeletal muscle, mitochondrial ATP production, glucose disposal, hyperinsulinemic-euglycemic clamp, chemiluminescence
- MeSH terms
- Adenosine Triphosphate, Adult, Biopsy, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Insulin, Male, Middle Aged, Mitochondria, Muscle, Obesity, Reference Values, Body Mass Index, Reactive Oxygen Species
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