title: Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats.
abstract: OBJECTIVE
  We investigated the effect of the selective sodium-dependent glucose cotransporter 2 inhibitor ipragliflozin on the simultaneous progression of diabetic microvascular complications of retinopathy, nephropathy and neuropathy in individual Spontaneously Diabetic Torii (SDT) fatty rats.
  
  
  METHODS
  Ipragliflozin was administered to male SDT fatty rats for 12weeks. Male Sprague-Dawley rats of the same age were used as non-diabetic controls. Non-fasting plasma glucose and glycated hemoglobin levels were measured every 4weeks. Cataract formation was monitored once a week, and the electroretinogram was measured after 6weeks of treatment. After the treatment period, motor nerve conduction velocity was measured and urinalysis was conducted. Tissue samples were then dissected for histopathological examination.
  
  
  RESULTS
  Treatment with ipragliflozin reduced glycated hemoglobin levels, inhibited the progression of cataract formation, prevented the prolongation of oscillatory potential peaks in the electroretinogram, ameliorated the slowing of motor nerve conduction velocity, and reduced the severity of glomerulosclerosis in SDT fatty rats.
  
  
  CONCLUSIONS
  These results suggest that the control of hyperglycemia with ipragliflozin slows the progression of the diabetic complications of retinopathy, nephropathy, and neuropathy.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, Japan. Electronic address: shoji.takakura@astellas.com.
authors.forename: Shoji
authors.initials: S
authors.lastname: Takakura
authors.affiliation: Nihon Bioresearch Inc., Hashima-shi, Gifu, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Toyoshi
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hayashizaki
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takasu
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D018450:Disease Progression; D005960:Glucosides / Q000494:pharmacology*; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D005960:Glucosides; D007004:Hypoglycemic Agents; C490300:Slc5a2 protein, rat; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; C572941:ipragliflozin
keywords: Cataract; Diabetic microvascular complications; Ipragliflozin L-proline (PubChem CID: 57339444); Nephropathy; Neuropathy; Retinopathy; Sodium-dependent glucose cotransporter 2; Type 2 diabetes mellitus