title: Effects of sodium-glucose cotransporter 2 selective inhibitor ipragliflozin on hyperglycaemia, oxidative stress, inflammation and liver injury in streptozotocin-induced type 1 diabetic rats.
abstract: OBJECTIVE
  Sodium-glucose cotransporter (SGLT) 2 plays an important role in renal glucose reabsorption and has been highlighted as a therapeutic target for the treatment of diabetes. Here, we investigated the therapeutic effects of SGLT2 selective inhibitor ipragliflozin in type 1 diabetic rats.
  
  
  METHODS
  Type 1 diabetic rats were prepared by intravenous administration of streptozotocin (STZ). Ipragliflozin was acutely or chronically administered, and therapeutic effects were investigated.
  
  
  RESULTS
  Single administration of ipragliflozin significantly increased urinary glucose excretion, and its effect lasted over 12 h. In addition, ipragliflozin improved glucose tolerance and sustainably reduced hyperglycaemia. Repeated administration of ipragliflozin to diabetic rats for 4 weeks significantly improved not only hyperglycaemia, but also hyperlipidaemia and hepatic steatosis with concomitant increases in urinary glucose excretion. In addition, ipragliflozin ameliorates renal glomerular hyperfiltration and albuminuria. Further, ipragliflozin reduced liver levels of oxidative stress biomarkers and plasma levels of inflammatory markers, and improved liver injury as assessed by plasma levels of aminotransferases.
  
  
  CONCLUSIONS
  These results suggest that SGLT2 selective inhibitor ipragliflozin exerts a beneficial effect on glycaemic control and ameliorates diabetes-associated metabolic abnormalities and complications in STZ-induced diabetic rats, and would be a potential agent for the treatment of type 1 diabetes.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Tahara
authors.forename: Eiji
authors.initials: E
authors.lastname: Kurosaki
authors.forename: Masanori
authors.initials: M
authors.lastname: Yokono
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamajuku
authors.forename: Rumi
authors.initials: R
authors.lastname: Kihara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takasu
authors.forename: Masakazu
authors.initials: M
authors.lastname: Imamura
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomiyama
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Noda
authors.forename: Masao
authors.initials: M
authors.lastname: Sasamata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shibasaki
mesh_terms: D000419:Albuminuria / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D018149:Glucose Intolerance / Q000188:drug therapy / Q000209:etiology; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000188:drug therapy* / Q000209:etiology; D006949:Hyperlipidemias / Q000188:drug therapy / Q000209:etiology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013311:Streptozocin; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; C572941:ipragliflozin; D013311:Streptozocin
keywords: SGLT2; diabetes; hyperglycaemia; ipragliflozin; urinary glucose excretion