Title:Sodium-glucose Cotransporter Type 2 Inhibitors: A New Insight into the Molecular
Mechanisms of Diabetic Nephropathy
Volume: 28
Issue: 26
Author(s): Na Li and Hong Zhou*
Affiliation:
- Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
Keywords:
Sodium-glucose cotransporter 2 inhibitors, diabetic nephropathy, renal protection, molecular mechanism, renal hypoxia, podocyte protection.
Abstract: Diabetic nephropathy is one of the chronic microvascular complications of diabetes and is a leading
cause of end-stage renal disease. Fortunately, clinical trials have demonstrated that sodium-glucose cotransporter
type 2 inhibitors could decrease proteinuria and improve renal endpoints and are promising agents for the
treatment of diabetic nephropathy. The renoprotective effects of sodium-glucose cotransporter type 2 inhibitors
cannot be simply attributed to their advantages in aspects of metabolic benefits, such as glycemic control, lowering
blood pressure, and control of serum uric acid, or improving hemodynamics associated with decreased
glomerular filtration pressure. Some preclinical evidence suggests that sodium-glucose cotransporter type 2
inhibitors exert their renoprotective effects by multiple mechanisms, including attenuation of oxidative and
endoplasmic reticulum stresses, anti-fibrosis and anti-inflammation, protection of podocytes, suppression of
megalin function, improvement of renal hypoxia, restored mitochondrial dysfunction and autophagy, as well as
inhibition of sodium-hydrogen exchanger 3. In the present study, the detailed molecular mechanisms of
sodium-glucose cotransporter type 2 inhibitors with the actions of diabetic nephropathy were reviewed, with the
purpose of providing the basis for drug selection for the treatment of diabetic nephropathy.
