Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus
Open accessAbstract
Low levels of physical activity and the presence of obesity are associated with mitochondrial dysfunction. In addition, mitochondrial dysfunction has been associated with the development of insulin resistance and type 2 diabetes mellitus (T2DM). Although the evidence for a causal relationship between mitochondrial function and insulin resistance is still weak, emerging evidence indicates that boosting mitochondrial function might be beneficial to patient health. Exercise training is probably the most recognized promoter of mitochondrial function and insulin sensitivity and hence is still regarded as the best strategy to prevent and treat T2DM. Animal data, however, have revealed several new insights into the regulation of mitochondrial metabolism, and novel targets for interventions to boost mitochondrial function have emerged. Importantly, many of these targets seem to be regulated by factors such as nutrition, ambient temperature and circadian rhythms, which provides a basis for nonpharmacological strategies to prevent or treat T2DM in humans. Here, we will review the current evidence that mitochondrial function can be targeted therapeutically to improve insulin sensitivity and to prevent T2DM, focusing mainly on human intervention studies.
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The PI3K/AKT Pathway in Obesity and Type 2 Diabetes
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“Excessive fatty acid oxidation in the mitochondria via the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC) increases the production of fatty acid metabolites and reactive oxygen species (ROS), subsequently activated intracellular stress kinases to inhibit IRS-1 and possibly exerting effects on in…”
BackgroundMetabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
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- Authors
- Hesselink, M. K. C., Schrauwen-Hinderling, V., & Schrauwen, P.
- Affiliations
- Maastricht University Medical Centre (NL)
- Corresponding author
- Schrauwen, Patrick
- Venue
- Nature Reviews Endocrinology
- Published
- 2016-07-22
- Volume
- 12
- Issue
- 11
- Pages
- 633-645
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W2502246205
- Cited by
- 242
- References
- 162
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 17 · 2023: 25 · 2022: 23 · 2021: 24 · 2020: 34 · 2019: 27 · 2018: 34 · 2017: 26 · 2016: 3 · 2013: 1
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- 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, insulin resistance, insulin sensitivity, exercise training, non-pharmacological treatment, nutrition, ambient temperature, circadian rhythm, obesity, mitochondrial metabolism, therapeutic target
- MeSH terms
- Carnitine, Circadian Rhythm, Diabetes Mellitus, Type 2, Diet Therapy, Exercise Therapy, Humans, Insulin Resistance, Mitochondria, Muscle, Obesity, Sleep, Temperature, Exercise, Cryotherapy, Muscle, Skeletal, Dietary Supplements, Caloric Restriction
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