Antidiabetic effects of SGLT2-selective inhibitor ipragliflozin in streptozotocin-nicotinamide-induced mildly diabetic mice

Atsuo Tahara, Eiji Kurosaki, Masanori Yokono, Daisuke Yamajuku, Rumi Kihara, Yuka Hayashizaki, Toshiyuki Takasu, Masakazu Imamura, Li Qun, Hiroshi Tomiyama, Yoshinori Kobayashi, Atsushi Noda, Masao Sasamata, Masayuki Shibasaki
Journal of Pharmacological Sciences 2012, 120 (1): 36-44
Sodium-glucose cotransporter (SGLT) 2 plays an important role in renal glucose reabsorption, and inhibition of renal SGLT2 activity represents an innovative strategy for the treatment of hyperglycemia in diabetic patients. The present study investigated the antidiabetic effects of ipragliflozin, a SGLT2-selective inhibitor, in streptozotocin-nicotinamide-induced mildly diabetic mice, which exhibited a mild decline in glucose tolerance associated with the loss of early-phase insulin secretion. Oral administration of ipragliflozin increased urinary glucose excretion in a dose-dependent manner, an effect which was significant at doses of 0.3 mg/kg or higher and lasted over 12 h. In addition, ipragliflozin dose-dependently improved hyperglycemia and glucose intolerance with concomitant decreases in plasma insulin levels without causing hypoglycemia. Once-daily dosing of ipragliflozin (0.1 - 3 mg/kg) for 4 weeks attenuated hyperglycemia, glucose intolerance, and impaired insulin secretion. These results suggest that the SGLT2-selective inhibitor ipragliflozin increases urinary glucose excretion by inhibiting renal glucose reabsorption, improves hyperglycemia in streptozotocin-nicotinamide-induced mildly diabetic mice, and may be useful for treating type 2 diabetes.

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