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Title

Sodium‐glucose co‐transporters and diabetic nephropathy: Is there a link with toll‐like receptors?

Authors

Ashrafi Jigheh, Zahra; Ghorbani Haghjo, Amir; Argani, Hassan; Sanajou, Davoud

Abstract

The incidence of diabetes mellitus (DM) has increased alarmingly over the last decades. Despite taking measures aimed at controlling hyperglycaemia and blood pressure, the rate of end‐stage renal disease (ESRD) is continually growing. Upon increased amounts of advanced glycation end products (AGEs) and their correspondent receptors (RAGEs), AGE‐RAGE axis is over‐activated in DM, being the first step in the initiation and propagation of inflammatory cascades. Meanwhile, HMGB1, released from damaged cells in the diabetic kidneys, is the most notable ligand for the highly expressed toll‐like receptors (TLRs) and RAGEs. TLRs play an indispensable role in the pathogenesis of diabetic nephropathy. Sodium‐glucose co‐transporter 2 (SGLT‐2) inhibitors are hypoglycaemic agents acting on the renal proximal tubules to prevent glucose reabsorption and therefore increase urinary glucose excretion. Besides improving glycaemic control, these hypoglycaemic agents possess direct renoprotective properties. Here, therefore, we review the most recent findings regarding interrelationship between SGLT2 inhibitors and HMGB1‐TLR4 axis.

Subjects

TOLL-like receptors; SALT-free diet; DIABETIC nephropathies; ADVANCED glycation end-products; GLYCEMIC control; CHRONIC kidney failure; KIDNEY tubules

Publication

Clinical & Experimental Pharmacology & Physiology, 2020, Vol 47, Issue 6, p919

ISSN

0305-1870

Publication type

Academic Journal

DOI

10.1111/1440-1681.13261