Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes.
Open accessAbstract
OBJECTIVE— Reduced mitochondrial capacity in skeletal muscle occurs in type 2 diabetic patients and in those at increased risk for this disorder, but the extent to which mitochondrial dysfunction in type 2 diabetic patients is remediable by physical activity and weight loss intervention is uncertain. We sought to address whether an intervention of daily moderate-intensity exercise combined with moderate weight loss can increase skeletal muscle mitochondrial content in type 2 diabetic patients and to address the relationship with amelioration of insulin resistance and hyperglycemia. RESEARCH DESIGN AND METHODS— Muscle biopsies were obtained before and after a 4-month intervention to assess mitochondrial morphology, mitochondrial DNA content, and mitochondrial enzyme activities. Glucose control, body composition, aerobic fitness, and insulin sensitivity were measured. RESULTS— In response to a weight loss of 7.1 ± 0.8% and a 12 ± 1.6% improvement in Vo2max (P < 0.05), insulin sensitivity improved by 59 ± 21% (P < 0.05). There were significant increases in skeletal muscle mitochondrial density (by 67 ± 17%, P < 0.01), cardiolipin content (55 ± 17%, P < 0.01), and mitochondrial oxidation enzymes. Energy expenditure during physical activity correlated with the degree of improvement in insulin sensitivity (r = 0.84, P < 0.01), and, in turn, improvement in mitochondrial content was a strong correlate of intervention-induced improvement in A1C and fasting plasma glucose. CONCLUSIONS— Intensive short-term lifestyle modifications can restore mitochondrial content and functional capacity in skeletal muscle in type 2 diabetic patients. The improvement in the oxidative capacity of skeletal muscle may be a key component mediating salutary effects of lifestyle interventions on hyperglycemia and insulin resistance.
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Mitochondrial content was determined by mitochondrial volume density measured by standard stereological methods.
“Mitochondrial content was determined by the parameter of mitochondrial volume density measured by standard stereological methods (19, 20) as in our previous studies (17, 18, 21).”
Even in the insulin-resistant state, skeletal muscle mitochondria respond to training.
“In fact, we have shown that even in the insulin-resistant state, skeletal muscle mitochondria respond to training (17, 18, 21).”
In patients with type 2 diabetes, walking and ergometer cycling increase mitochondrial muscle respiration, mitochondrial content and density, and oxidative enzyme activity.
“In patients with T2DM, walking and ergometer cycling exercise increased mitochondrial muscle respiration and mitochondrial content and density, as well as the activity of oxidative enzymes214,215.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [214]
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- Authors
- Toledo, F. G. S., Menshikova, E. V., Ritov, V. B., Azuma, K., Radikova, Z., DeLany, J., & Kelley, D. E.
- Affiliations
- University of Pittsburgh (US)
- From the Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-08-01
- Volume
- 56
- Issue
- 8
- Pages
- 2142-2147
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2127262263
- Cited by
- 321
- References
- 39
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 12 · 2023: 17 · 2022: 17 · 2021: 15 · 2020: 15 · 2019: 17 · 2018: 15 · 2017: 16 · 2016: 12 · 2015: 11 · 2014: 13 · 2013: 20 · 2012: 17
- FWCI
- 19.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- University of Pittsburgh (M01RR00056)
- Slovenská Akadémia Vied
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK-462, DK-49200-08, R01DK049200)
- National Center for Research Resources (M01RR000056, 5 M01 RR00056)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- 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
- Keywords
- type 2 diabetes, skeletal muscle mitochondria, mitochondrial dysfunction, physical activity, weight loss, exercise intervention, insulin resistance, glycemic control, mitochondrial DNA content, cardiolipin, mitochondrial enzyme activity, cardiorespiratory fitness, energy expenditure, hyperglycemia, lifestyle modification
- MeSH terms
- Adult, Biopsy, Blood Glucose, Diabetes Mellitus, Type 2, Exercise Therapy, Humans, Insulin, Middle Aged, Mitochondria, Weight Loss, Muscle, Skeletal, Microscopy, Electron, Transmission
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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