1. Academic Validation
  2. Long-term treatment with sergliflozin etabonate improves disturbed glucose metabolism in KK-A(y) mice

Long-term treatment with sergliflozin etabonate improves disturbed glucose metabolism in KK-A(y) mice

  • Eur J Pharmacol. 2009 Sep 15;618(1-3):98-104. doi: 10.1016/j.ejphar.2009.07.001.
Kenji Katsuno 1 Yoshikazu Fujimori Yukiko Ishikawa-Takemura Masayuki Isaji
Affiliations

Affiliation

  • 1 Discovery Research Laboratory II, R&D, Kissei Pharmaceutical Co Ltd, Azumino, Japan. kenji_katsuno@pharm.kissei.co.jp
Abstract

Sergliflozin etabonate, a novel oral selective low-affinity sodium glucose cotransporter (SGLT2) inhibitor, improves hyperglycemia by suppressing renal glucose reabsorption, in which SGLT2 participates as a dominant transporter. In the present study, we examined the antidiabetic profile of sergliflozin etabonate in a diabetic model, KK-A(y) mice, with symptoms of obesity and hyperinsulinemia. The blood glucose level was monitored in non-fasted female KK-A(y) mice after a single oral administration of sergliflozin etabonate. The non-fasting blood glucose level was reduced in a dose-dependent manner after a single oral administration of sergliflozin etabonate (39% reduction at 2 h after a dose of 30 mg/kg). The effects of long-term administration of sergliflozin etabonate on the blood glucose level were assessed in female KK-A(y) mice in several studies (4-day, 8-week, and 9-week administration study), in which sergliflozin etabonate was administered in the diet. The non-fasting blood glucose and plasma Insulin were both lowered dose-dependently in the 4-day administration study. Long-term treatment with sergliflozin etabonate dose-dependently improved the hyperglycemia and prevented body weight gain in the 8-week study. In addition to the improvement in glycemic control, fatty liver and pancreatic beta-cell abnormalities were ameliorated in mice fed sergliflozin etabonate in the 9-week study. These data indicate that SGLT2 inhibitors could be useful to improve hyperglycemia resulting from Insulin resistance without pancreatic beta-cell abuse or body weight gain. SGLT2 inhibitors may simultaneously realize both a systemic negative energy balance and correction of hyperglycemia.

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