title: Tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2, suppresses renal damage in KKAy/Ta mice, obese and type 2 diabetic animals.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishibashi
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan shoichi@med.kurume-u.ac.jp.
authors.forename: Sho-Ichi
authors.initials: SI
authors.lastname: Yamagishi
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000419:Albuminuria / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005960:Glucosides / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C490299:Slc5a2 protein, mouse; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000118:Acetylglucosaminidase; C575086:6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
keywords: Diabetic nephropathy; sodium-glucose cotransporter 2; tofogliflozin; tubular injury