Crosstalk Between Sodium-Glucose Cotransporter Inhibitors and
Sodium-Hydrogen Exchanger- 1 and 3 in Cardiometabolic Diseases
Abstract
The hallmark of type 2 diabetes mellitus (T2DM) is abnormal glucose
homeostasis due to hyperglycaemia or insulin resistance. Metabolic
abnormalities in T2DM lead to cellular dysfunction and the development
of diabetic cardiomyopathy and heart failure. New antihyperglycemic
agents, such as glucagon-like peptide-1 receptor agonists and the
sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown to
attenuate endothelial dysfunction at the cellular level. In addition,
they showed cardiovascular safety and cardioprotective effects. How
these drugs exert their cardioprotective effects is unknown, although
recent studies show that cardiovascular homeostasis occurs through the
interplay of the sodium hydrogen exchangers (NHE), specifically NHE1 and
NHE3 with SGLT2i. Another theoretical explanation for the SGLT2i
cardioprotective effects is through natriuresis by the kidney. This
theory highlights the possible involvement of renal NHE transporters in
the management of heart failure. This review outlines possible
mechanisms predisposing to diabetic cardiomyopathy and discusses the
interaction between NHE and SGLT2i in cardiovascular disease.