Effects of sodium-glucose cotransporter 2 selective inhibitor ipragliflozin on hyperglycaemia, oxidative stress, inflammation and liver injury in streptozotocin-induced type 1 diabetic rats

Atsuo Tahara, Eiji Kurosaki, Masanori Yokono, Daisuke Yamajuku, Rumi Kihara, Yuka Hayashizaki, Toshiyuki Takasu, Masakazu Imamura, Qun Li, Hiroshi Tomiyama, Yoshinori Kobayashi, Atsushi Noda, Masao Sasamata, Masayuki Shibasaki
Journal of Pharmacy and Pharmacology 2014, 66 (7): 975-87

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.

KEY FINDINGS: 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.

CONCLUSION: 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.

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