SGLT2 inhibitor ipragliflozin exerts antihyperglycemic effects via the blood glucose-dependent increase in urinary glucose excretion in type 2 diabetic mice

Abstract

This study investigated the antihyperglycemic effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin via the blood glucose-dependent increase in urinary glucose excretion in KK/Ay type 2 diabetic mice. In oral glucose tolerance tests (glucose load: 1, 2, or 4 g/kg) in 24-h-fasted mice, blood glucose levels increased in a glucose-loading dose-dependent manner. Oral administration of ipragliflozin (1 mg/kg) significantly inhibited the increase in blood glucose concomitant with urinary glucose excretion. To investigate the effects of ipragliflozin under low blood glucose conditions, blood glucose level and urinary glucose excretion were examined under fasting conditions in diabetic mice that had prefasted for 0, 6, 12, 18, or 24 h. Ipragliflozin significantly lowered blood glucose levels in mice that had prefasted for 0, 6, or 12 h, but not 18 h or more. Blood glucose level was well correlated with ipragliflozin-induced antihyperglycemic and urinary glucose excretion effects, suggesting that these effects occur in a blood glucose-dependent manner. Thus, in a hyperglycemic state, ipragliflozin exerts a potent antihyperglycemic effect and marked increases in urinary glucose excretion; however, in a non-hyperglycemic or hypoglycemic state, the hypoglycemic effect is weak. Ipragliflozin may therefore be a useful antidiabetic agent for normalizing daily blood glucose fluctuations in type 2 diabetes.