The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans
Open accessAbstract
Aims/hypothesisWe sought to evaluate if the cellular localisation and molecular species of diacylglycerol (DAG) were related to insulin sensitivity in human skeletal muscle.MethodsHealthy sedentary obese controls (Ob; n = 6; mean±SEM age 39.5 ± 2.3 years; mean±SEM BMI 33.3 ± 1.4 kg/m2), individuals with type 2 diabetes (T2D; n = 6; age 44 ± 1.8 years; BMI 30.1 ± 2.3 kg/m2), and lean endurance-trained athletes (Ath; n = 10; age 35.4 ± 3.1 years; BMI 23.3 ± 0.8 kg/m2) were studied. Insulin sensitivity was determined using an IVGTT. Muscle biopsy specimens were taken after an overnight fast, fractionated using ultracentrifugation, and DAG species measured using liquid chromatography/MS/MS.ResultsTotal muscle DAG concentration was higher in the Ob (mean±SEM 13.3 ± 1.0 pmol/μg protein) and T2D (15.2 ± 1.0 pmol/μg protein) groups than the Ath group (10.0 ± 0.78 pmol/μg protein, p = 0.002). The majority (76–86%) DAG was localised in the membrane fraction for all groups, but was lowest in the Ath group (Ob, 86.2 ± 0.98%; T2D, 84.2 ± 1.2%; Ath, 75.9 ± 2.7%; p = 0.008). There were no differences in cytoplasmic DAG species (p > 0.12). Membrane DAG species C18:0/C20:4, Di-C16:0 and Di-C18:0 were significantly more abundant in the T2D group. Cytosolic DAG species were negatively related to activation of protein kinase C (PKC)ε but not PKCθ, whereas membrane DAG species were positively related to activation of PKCε, but not PKCθ. Only total membrane DAG (r = −0.624, p = 0.003) and Di-C18:0 (r = −0.595, p = 0.004) correlated with insulin sensitivity. Disaturated DAG species were significantly lower in the Ath group (p = 0.001), and significantly related to insulin sensitivity (r = −0.642, p = 0.002).Conclusions/interpretationThese data indicate that both cellular localisation and composition of DAG influence the relationship to insulin sensitivity. Our results suggest that only saturated DAG in skeletal muscle membranes are related to insulin resistance in humans.
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PKC-θ knockout mice are protected from fat-induced insulin resistance
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“Notably, in addition to composition, the insulin-desensitising effects of DAG may be governed by its subcellular location [17].”
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Cited by
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Kalinkovich, A., & Livshits, G. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.008 · Cited by 882
Role of diacylglycerol activation of PKCθ in lipid-induced muscle insulin resistance in humans
Szendroedi, J., Yoshimura, T., Phielix, E., Koliaki, C., Marcucci, M., Zhang, D., Jelenik, T., Müller, J., Herder, C., Nowotny, P., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409229111 · Cited by 415
Role of intramyocelluar lipids in human health
Coen, P. M., & Goodpaster, B. H. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.05.009 · Cited by 252
Perreault, L., Newsom, S. A., Strauss, A., Kerege, A., Kahn, D. E., Harrison, K. A., Snell-Bergeon, J. K., Nemkov, T., D’Alessandro, A., Jackman, M. R., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.96805 · Cited by 184
Self-citation
Metadata
- Authors
- Bergman, B. C., Hunerdosse, D. M., Kerege, A., Playdon, M. C., & Perreault, L.
- Venue
- Diabetologia
- Published
- 2012-01-15
- Volume
- 55
- Issue
- 4
- Pages
- 1140-1150
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2036841744
- Cited by
- 158
- References
- 12
- FWCI
- 10.35
- Type
- journal article
- Language
- en
- Open access
- bronze
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