New findings implicate sodium transport in α-cell secretory dysfunction, leading to impaired counter-regulatory responses in diabetes. However, these findings also raise important questions about the tissue-specific roles of sodium transport and suggest that inhibitors of sodium transport may have potentially divergent roles in the pancreas, kidney and heart.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank
International Journal of Obesity Open Access 16 July 2020
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Knudsen, J. G. et al. Dysregulation of glucagon secretion by hyperglycemia-induced sodium-dependent reduction of ATP production. Cell Metab. https://doi.org/10.1016/j.cmet.2018.10.003 (2018).
Suga, T. et al. SGLT1 in pancreatic alpha cells regulates glucagon secretion in mice, possibly explaining the distinct effects of SGLT2 inhibitors on plasma glucagon levels. Mol. Metab. https://doi.org/10.1016/j.molmet.2018.10.009 (2018).
Bonner, C. et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat. Med. 21, 512–517 (2015).
Pessoa, T. D. et al. Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule. J. Am. Soc. Nephrol. 25, 2028–2039 (2014).
Layton, A. T., Vallon, V. & Edwards, A. Modeling oxygen consumption in the proximal tubule: effects of NHE and SGLT2 inhibition. Am. J. Physiol. Renal Physiol. 308, F1343–F1357 (2015).
Lytvyn, Y. et al. Sodium glucose cotransporter-2 inhibition in heart failure: potential mechanisms, clinical applications, and summary of clinical trials. Circulation 136, 1643–1658 (2017).
von Lewinski, D. et al. Functional effects of glucose transporters in human ventricular myocardium. Eur. J. Heart Fail. 12, 106–113 (2010).
Ye, Y. et al. Dapagliflozin attenuates Na+/H+ exchanger-1 in cardiofibroblasts via AMPK activation. Cardiovasc. Drugs Ther. 32, 553–558 (2018).
Baartscheer, A. et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia 60, 568–573 (2018).
Packer, M. et al. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action. JAMA Cardiol. 2, 1025–1029 (2017).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
J.A.L. has received consulting fees and/or speaking honorarium from Boehringer Ingelheim, Prometic, Intarcia Therapeutics, Inc., Novo Nordisk, Eli Lilly & Co, Merck and AstraZeneca, and has received operating grant support from Merck and Sanofi. D.Z.C. has received consulting fees and/or speaking honorarium from Janssen, Boehringer Ingelheim-Eli, Lilly, AstraZeneca, Merck, Sanofi and Prometic, and has received operating funds from Janssen, Boehringer Ingelheim-Eli, Lilly, AstraZeneca and Merck.
Rights and permissions
About this article
Cite this article
Lovshin, J.A., Cherney, D.Z. Sodium transport in diabetes: two sides to the coin. Nat Rev Nephrol 15, 125–126 (2019). https://doi.org/10.1038/s41581-018-0106-3
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41581-018-0106-3
This article is cited by
-
Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank
International Journal of Obesity (2020)
