The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Insulin Stimulates Mitochondrial Fusion and Function in Cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 Signaling Pathway
Open accessAbstract
Insulin regulates heart metabolism through the regulation of insulin-stimulated glucose uptake. Studies have indicated that insulin can also regulate mitochondrial function. Relevant to this idea, mitochondrial function is impaired in diabetic individuals. Furthermore, the expression of Opa-1 and mitofusins, proteins of the mitochondrial fusion machinery, is dramatically altered in obese and insulin-resistant patients. Given the role of insulin in the control of cardiac energetics, the goal of this study was to investigate whether insulin affects mitochondrial dynamics in cardiomyocytes. Confocal microscopy and the mitochondrial dye MitoTracker Green were used to obtain three-dimensional images of the mitochondrial network in cardiomyocytes and L6 skeletal muscle cells in culture. Three hours of insulin treatment increased Opa-1 protein levels, promoted mitochondrial fusion, increased mitochondrial membrane potential, and elevated both intracellular ATP levels and oxygen consumption in cardiomyocytes in vitro and in vivo. Consequently, the silencing of Opa-1 or Mfn2 prevented all the metabolic effects triggered by insulin. We also provide evidence indicating that insulin increases mitochondrial function in cardiomyocytes through the Akt-mTOR-NFκB signaling pathway. These data demonstrate for the first time in our knowledge that insulin acutely regulates mitochondrial metabolism in cardiomyocytes through a mechanism that depends on increased mitochondrial fusion, Opa-1, and the Akt-mTOR-NFκB pathway.
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Cites
Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211046 · Cited by 2,601
Mitochondrial dysfunction and type 2 diabetes
Lowell, B. B., & Shulman, G. I. (2005) · Science · doi:10.1126/science.1104343 · Cited by 2,070
Claycomb, W. C., Lanson, N. A., Stallworth, B. S., Egeland, D. B., Delcarpio, J. B., Bahinski, A., & Izzo, N. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.2979 · Cited by 1,546
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Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism
Bach, D., Pich, S., Soriano, F. X., Vega, N., Baumgartner, B., Oriola, J., Daugaard, J. R., Lloberas, J., Camps, M., Zierath, J. R., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212754200 · Cited by 832 · cited 2×
“AsMfn2 and microOpa-1 (both Ad5 serotype) generation and use was as previously described (14).”
MethodSelf-citationInsulin Resistance and Hyperinsulinemia
Shanik, M. H., Xu, Y., Škrha, J., Dankner, R., Zick, Y., & Roth, J. (2008) · Diabetes Care · doi:10.2337/dc08-s264 · Cited by 791
Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion
Song, Z., Ghochani, M., McCaffery, J. M., Frey, T. G., & Chan, D. C. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-03-0252 · Cited by 623 · cited 1×
“In mammalian cells, Mfn and Opa-1 are the main regulators of mitochondrial fusion (28).”
Mitochondrial Energetics in the Heart in Obesity-Related Diabetes
Boudina, S., Sena, S., Theobald, H., Sheng, X., Wright, J. J., Hu, X. X., Aziz, S., Johnson, J. I., Bugger, H., Zaha, V. G., et al. (2007) · Diabetes · doi:10.2337/db07-0481 · Cited by 586
Self-citationBoudina, S., Sena, S., O’Neill, B. T., Tathireddy, P., Young, M. E., & Abel, E. D. (2005) · Circulation · doi:10.1161/circulationaha.105.554360 · Cited by 502
Self-citationPich, S., Bach, D., Briones, P., Liesa, M., Camps, M., Testar, X., Palacín, M., & Zorzano, A. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi149 · Cited by 455
Cited by
Cardiac Energy Metabolism in Heart Failure
Lopaschuk, G. D., Karwi, Q. G., Tian, R., Wende, A. R., & Abel, E. D. (2021) · Circulation Research · doi:10.1161/circresaha.121.318241 · Cited by 1,373
Self-citationMitochondrial Dynamics and Metabolic Regulation
Wai, T., & Langer, T. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.12.001 · Cited by 1,300
Mitochondrial dynamics, mitophagy and cardiovascular disease
Vásquez‐Trincado, C., García‐Carvajal, I., Pennanen, C., Parra, V., Hill, J. A., Rothermel, B. A., & Lavandero, S. (2016) · The Journal of Physiology · doi:10.1113/jp271301 · Cited by 629
Self-citationLiu, Y. J., McIntyre, R. L., Janssens, G. E., & Houtkooper, R. H. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111212 · Cited by 334
Ong, S.-B., Samangouei, P., Kalkhoran, S. B., & Hausenloy, D. J. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.11.005 · Cited by 323
Metadata
- Authors
- Parra, V., Verdejo, H. E., Iglewski, M., del Campo, A., Troncoso, R., Jones, D., Zhu, Y., Kuzmicic, J., Pennanen, C., Lopez‑Crisosto, C., Jaña, F., Ferreira, J., Noguera, E., Chiong, M., Bernlohr, D. A., Klip, A., Hill, J. A., Rothermel, B. A., Abel, E. D., Zorzano, A., & Lavandero, S.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2013-12-13
- Volume
- 63
- Issue
- 1
- Pages
- 75-88
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2154726349
- Cited by
- 218
- References
- 14
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Parra, V., Verdejo, H. E., Iglewski, M., del Campo, A., Troncoso, R., Jones, D., Zhu, Y., Kuzmicic, J., Pennanen, C., Lopez‑Crisosto, C., Jaña, F., Ferreira, J., Noguera, E., Chiong, M., Bernlohr, D. A., Klip, A., Hill, J. A., Rothermel, B. A., Abel, E. D., . . . Lavandero, S. (2014). Insulin Stimulates Mitochondrial Fusion and Function in Cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 Signaling Pathway. Diabetes. https://doi.org/10.2337/db13-0340
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
