SGLT2 Inhibitors: The First Endothelial-Protector for Diabetic Nephropathy

Area of Science:

• Nephrology
• Cardiology
• Endocrinology
• Pharmacology

Background:

• Sodium-glucose co-transporter type 2 inhibitors (SGLT2i) are used for diabetic nephropathy and cardiopathy.
• Previous observations linked nephroprotective effects to reduced glomerular filtration rate (GFR) and cardioprotective functions.
• SGLT2i may have extratubular effects beyond glycosuria and natriuria, particularly influencing mitochondrial function in diabetes.

Purpose of the Study:

• To explore the broader therapeutic effects of SGLT2 inhibitors beyond hemodynamic modulation.
• To investigate the role of SGLT2 inhibitors in endothelial function and their potential as endothelial-protective drugs.
• To examine the correlation between albumin-creatinine ratio (ACR) reduction and mitochondrial activity in glomerular endothelial cells.

Main Methods:

• Review of existing literature on SGLT2 inhibitors, nephroprotective agents, and their effects on GFR, hemoglobin, and mitochondrial function.
• Analysis of evidence regarding SGLT2 expression in atypical regions under pathological conditions.
• Investigation into the impact of SGLT2 inhibition on intracellular glucose accumulation in endothelial cells.

Main Results:

• SGLT2 inhibitors are identified as the first class of endothelial-protective drugs, preventing glucose accumulation in aberrantly expressing SGLT2 in Type 2 Diabetes mellitus (T2DM) endothelial cells.
• SGLT2i share a GFR-reducing effect with other nephroprotective drugs, indicating a potential mechanism for optimal drug dosing.
• The anti-proteinuric effects of SGLT2i may involve direct actions on glomerular endothelial cells, potentially linked to mitochondrial function.

Conclusions:

• SGLT2 inhibitors offer novel endothelial protection by mitigating intracellular glucose overload in T2DM.
• The GFR-reducing effect of SGLT2 inhibitors suggests broader applications in managing ageing-related kidney disease.
• Further research into SGLT2i's impact on mitochondrial function and glomerular endothelial cells is warranted for understanding their full therapeutic potential.