Crosstalk between sodium–glucose cotransporter inhibitors and sodium–hydrogen exchanger 1 and 3 in cardiometabolic diseases

Al Anood Al-Shamasi, Rozina Elkaffash, Meram Mohamed, Menatallah Rayan, Dhabya Al-Khater, Alain Pierre Gadeau, Rashid Ahmed, Anwarul Hasan, Hussein Eldassouki, Huseyin Cagatay Yalcin, Muhammad Abdul-Ghani, Fatima Mraiche

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


Abnormality in glucose homeostasis due to hyperglycemia or insulin resistance is the hallmark of type 2 diabetes mellitus (T2DM). These metabolic abnormalities in T2DM lead to cellular dysfunction and the development of diabetic cardiomyopathy leading to heart failure. New anti-hyperglycemic agents including glucagon-like peptide-1 receptor agonists and the sodium–glucose cotransporter-2 inhibitors (SGLT2i) have been shown to attenuate endothelial dysfunction at the cellular level. In addition, they improved cardiovascular safety by exhibiting cardioprotective effects. The mechanism by which these drugs exert their cardioprotective effects is unknown, although recent studies have shown that cardiovascular homeostasis occurs through the interplay of the sodium–hydrogen exchangers (NHE), specifically NHE1 and NHE3, with SGLT2i. Another theoreti-cal explanation for the cardioprotective effects of SGLT2i is through natriuresis by the kidney. This theory highlights the possible involvement of renal NHE transporters in the management of heart fail-ure. This review outlines the possible mechanisms responsible for causing diabetic cardiomyopathy and discusses the interaction between NHE and SGLT2i in cardiovascular diseases.

Original languageEnglish (US)
Article number12677
JournalInternational journal of molecular sciences
Issue number23
StatePublished - Dec 1 2021


  • Cardiovascular diseases
  • Diabetes
  • NHE1
  • NHE3
  • SGLT1
  • SGLT2
  • Sodium–glucose cotransporter inhibitors
  • Sodium–hydrogen exchanger

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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