Tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2, suppresses renal damage in KKAy/Ta mice, obese and type 2 diabetic animals

Abstract

Objective: Inhibitors of sodium-glucose cotransporter 2 ameliorate hyperglycaemia in diabetes by increasing urinary glucose excretion. However, the effects of sodium-glucose cotransporter 2 inhibitors on tubulointerstitial damage in diabetic nephropathy are not fully elucidated. We examined whether tofogliflozin, an inhibitor of sodium-glucose cotransporter 2, suppressed renal damage in KKAy/Ta mice, obese and type 2 diabetic animals. Materials and methods: Male 8-week-old KKAy/Ta mice or control C57BL/6J mice were kept on a standard diet with or without 0.015% tofogliflozin for 5 weeks. Blood glucose and blood pressure, body and kidney weight, urinary N-acetyl-β-d-glucosaminidase activity and albumin excretion levels were monitored. Results: Although tofogliflozin treatment did not affect blood pressure, body weight or serum creatinine values, it improved hyperglycaemia and blocked the elevation of urinary N-acetyl-β-d-glucosaminidase activity in KKAy/Ta diabetic mice at 9, 11 and 13 weeks. Furthermore, compared with control mice, urinary albumin excretion levels and kidney weight were increased in 13-week-old KKAy/Ta mice, both of which were suppressed by the treatment with tofogliflozin. Conclusion: Our present results demonstrated that tofogliflozin could suppress albuminuria and tubulointerstitial injury in obese and type 2 diabetic mice. Inhibition of glucose entry into tubular cells by tofogliflozin may exert renoprotective properties in diabetes.