An SGLT2 inhibitor, canagliflozin, reduces blood glucose level in the renal capillaries and protects the capillary network in the diabetic rats.

Abstract

Aim: Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently demonstrate renal protection against progressive kidney disease. We hypothesised that SGLT2 inhibition reduces blood glucose levels in peri-proximal tubular capillaries by limiting reabsorption from the tubular filtrate, thereby safeguarding the renal microvasculature from hyperglycaemic stress.

Materials and methods: In anaesthetised streptozotocin-induced type 1 and Otsuka-Long Evans fatty (OLETF) type 2 diabetic rats, we measured the arterial-to-renal venous glucose ratio (RV/A) to evaluate the effects of canagliflozin, a SGLT2 inhibitor.

Results: In fasting OLETF rats, three-day oral canagliflozin treatment at both glycaemic and subglycaemic doses significantly lowered the RV/A glucose ratio compared with vehicle. During anaesthesia, duodenal glucose infusion increased the RV/A glucose ratio in diabetic OLETF rats, an effect prevented by canagliflozin but not by acute insulin infusion. Moreover, 4-week canagliflozin therapy preserved renal capillary density more effectively than insulin in OLETF rats.

Conclusion: These findings indicate that canagliflozin offers superior protection of the renal microvasculature from hyperglycaemic stress, independent of its systemic glucose-lowering action.