The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits
Open accessAbstract
Empagliflozin (EMPA), an inhibitor of the renal sodium–glucose cotransporter (SGLT) 2, reduces the risk of cardiovascular death in patients with type 2 diabetes. The underlying mechanism of this effect is unknown. Elevated cardiac cytoplasmic Na + ([Na + ] c ) and Ca 2+ ([Ca 2+ ] c ) concentrations and decreased mitochondrial Ca 2+ concentration ([Ca 2+ ] m ) are drivers of heart failure and cardiac death. We therefore hypothesised that EMPA would directly modify [Na + ] c , [Ca 2+ ] c and [Ca 2+ ] m in cardiomyocytes. [Na + ] c, [Ca 2+ ] c , [Ca 2+ ] m and Na + /H + exchanger (NHE) activity were measured fluorometrically in isolated ventricular myocytes from rabbits and rats. An increase in extracellular glucose, from 5.5 mmol/l to 11 mmol/l, resulted in increased [Na + ] c and [Ca 2+ ] c levels. EMPA treatment directly inhibited NHE flux, caused a reduction in [Na + ] c and [Ca 2+ ] c and increased [Ca 2+ ] m . After pretreatment with the NHE inhibitor, Cariporide, these effects of EMPA were strongly reduced. EMPA also affected [Na + ] c and NHE flux in the absence of extracellular glucose. The glucose lowering kidney-targeted agent, EMPA, demonstrates direct cardiac effects by lowering myocardial [Na + ] c and [Ca 2+ ] c and enhancing [Ca 2+ ] m , through impairment of myocardial NHE flux, independent of SGLT2 activity.
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Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504720 · Cited by 12,315
Cited by
SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review
Verma, S., & McMurray, J. J. V. (2018) · Diabetologia · doi:10.1007/s00125-018-4670-7 · Cited by 999
Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors
Lopaschuk, G. D., & Verma, S. (2020) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2020.02.004 · Cited by 894
Inzucchi, S. E., Zinman, B., Fitchett, D., Wanner, C., Ferrannini, E., Schumacher, M., Schmoor, C., Ohneberg, K., Johansen, O. E., George, J. T., et al. (2018) · Diabetes Care · doi:10.2337/dc17-1096 · Cited by 740
Wanner, C., Lachin, J. M., Inzucchi, S. E., Fitchett, D., Mattheus, M., George, J., Woerle, H. J., Broedl, U. C., von Eynatten, M., & Zinman, B. (2018) · Circulation · doi:10.1161/circulationaha.117.028268 · Cited by 469
Lytvyn, Y., Bjornstad, P., Udell, J. A., Lovshin, J. A., & Cherney, D. Z. I. (2017) · Circulation · doi:10.1161/circulationaha.117.030012 · Cited by 459
Metadata
- Authors
- Baartscheer, A., Schumacher, C. A., Wüst, R. C. I., Fiolet, J. W. T., Stienen, G. J. M., Coronel, R., & Zuurbier, C. J.
- Venue
- Diabetologia
- Published
- 2016-10-17
- Volume
- 60
- Issue
- 3
- Pages
- 568-573
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2538443876
- Cited by
- 661
- References
- 1
- FWCI
- 33.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Baartscheer, A., Schumacher, C. A., Wüst, R. C. I., Fiolet, J. W. T., Stienen, G. J. M., Coronel, R., & Zuurbier, C. J. (2017). Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia. https://doi.org/10.1007/s00125-016-4134-x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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