Mitochondrial involvement in skeletal muscle insulin resistance: A case of imbalanced bioenergetics
Open accessAbstract
Skeletal muscle insulin resistance in obesity associates with mitochondrial dysfunction, but the causality of this association is controversial. This review evaluates mitochondrial models of nutrient-induced muscle insulin resistance. It transpires that all models predict that insulin resistance arises as a result of imbalanced cellular bioenergetics. The nature and precise origin of the proposed insulin-numbing molecules differ between models but all species only accumulate when metabolic fuel supply outweighs energy demand. This observation suggests that mitochondrial deficiency in muscle insulin resistance is not merely owing to intrinsic functional defects, but could instead be an adaptation to nutrient-induced changes in energy expenditure. Such adaptive effects are likely because muscle ATP supply is fully driven by energy demand. This market-economic control of myocellular bioenergetics offers a mechanism by which insulin-signalling deficiency can cause apparent mitochondrial dysfunction, as insulin resistance lowers skeletal muscle anabolism and thus dampens ATP demand and, consequently, oxidative ATP synthesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Obesity is characterised by elevated levels of cytokines and fatty acids, and it is thought that elevated levels of both provoke insulin resistance.
“Obesity is characterised by elevated levels of cytokines and fatty acids, and it is thought that elevated levels of both provoke insulin resistance.94”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [94]
The consensus in the literature is that T2D clinical manifestation is provoked by peripheral tissue insulin resistance, which is in turn, usually induced by obesity.
“The consensus in the literature is that T2D clinical manifestation is provoked by peripheral tissue insulin resistance, which is in turn, usually induced by obesity.6,30,94”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [94]
It seems that a high rate of ATP turnover in athletes prevents skeletal muscle insulin resistance, but a decreased demand for ATP in typically sedentary obese individuals with and without T2D induces insulin resistance.
“Thus, it seems that a high rate of ATP turnover in athletes prevents skeletal muscle insulin resistance, but a decreased demand for ATP in typically sedentary obese individuals with and without T2D induces insulin resistance.94”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [94]
Chronic insulin resistance induced by obesity is pathological overall in metabolic syndrome, a syndrome characterised by disorders that collectively predispose risk to T2D and cardiovascular pathology.
“The general consensus in the literature is that chronic insulin resistance, induced by obesity, is thought to be pathological overall in the metabolic syndrome, which is a syndrome characterised by a range of disorders that collectively predispose risk to T2D and cardiovascular pathology.94”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [94]
Skeletal muscle insulin resistance has been associated with intracellular lipid accumulation.
“Skeletal muscle insulin resistance has been associated with intracellular lipid accumulation.94”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [94]
Adipose tissue likely contributes to T2D aetiology/pathogenesis, but extent remains unknown.
“Thus, the adipose tissue also likely contributes to T2D aetiology/pathogenesis, but to what extent remains currently unknown.94”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [94]
Increased fatty acid inflow leads to an increase in the ATP/ADP ratio in the mitochondria, along with a reduced electron transfer chain, resulting in inhibition of mitochondrial respiration, increase in ROS formation, myocyte toxicity, and finally, development of sarcopenia.
“Increased fatty acid inflow leads to an increase in the ATP/ADP ratio in the mitochondria, along with a reduced electron transfer chain. This then results in the inhibition of mitochondrial respiration, increase in ROS formation, myocyte toxicity, and finally, development of sarcopenia [29].”
From Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences (2020) · cites this paper as [29]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 282 · Cited by 67
Research works printed but not linked: 4
- D.G. Nicholls, S. Ferguson, Bioenergetics 4, Academic Press, London, 2013.
- D. Voet, J.G. Voet, Biochemistry, fourth ed. Wiley Global Education, 2010.
- K.L. Hoehn, A.B. Salmon, C. Hohnen-Behrens, N. Turner, A.J. Hoy, G.J. Maghzal, et al., Insulin resistance is a cellular antioxidant defense mechanism, Proc. Natl. Acad. Sci.
- C.S. Choi, D.B. Savage, L. Abu-Elheiga, Z.-X. Liu, S. Kim, A. Kulkarni, et al., Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy ex- penditure, reduces fat mass, and improves insulin sensitivity, Proc. Natl. Acad. Sci.
- Authors
- Affourtit, C.
- Affiliations
- University of Plymouth (GB)
- Corresponding author
- Affourtit, Charles
- ORCID
- Affourtit, Charles
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 1857
- Issue
- 10
- Pages
- 1678-1693
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2499591550
- Cited by
- 67
- References
- 282
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 8 · 2021: 13 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 10 · 2016: 1
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- PEARL (University of Plymouth) (submittedVersion)
- Funders
- Medical Research Council (G1100165)
- Daphne Jackson Trust
- Plymouth University (consumables)
- 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
- skeletal muscle insulin resistance, mitochondrial dysfunction, bioenergetics, obesity, insulin signaling, ATP demand, energy expenditure, muscle anabolism
- MeSH terms
- Animals, Energy Metabolism, Humans, Insulin, Insulin Resistance, Mitochondria, Signal Transduction, Muscle, Skeletal
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 ›
Are you an author, or do you see a problem with this page? Request a review
