Jpn. J. Pharmacol. 84 (3), 351-354 (2000)

Correction of Hyperglycemia and Insulin Sensitivity by T-1095, an Inhibitor of Renal Na⁺-Glucose Cotransporters, in Streptozotocin-Induced Diabetic Rats

Akira Oku¹, Kiichiro Ueta¹, Kenji Arakawa¹, Tomomi Kano-Ishihara¹, Takeshi Matsumoto¹, Tetsuya Adachi²,
Koichiro Yasuda³, Kinsuke Tsuda², Katsuo Ikezawa¹ and Akira Saito^1,*

¹Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan
²Laboratory of Metabolism, Kyoto University Graduate School of Human and Environmental Studies, Sakyo-ku, Kyoto 606-8501, Japan
³Laboratory of Metabolism, Faculty of Integrated Human Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
*Corresponding author.ﾊﾊFAX:+81-48-433-8161
E-mail: a-saito@tanabe.co.jp

Abstract: We investigated the effects of T-1095 (3-(benzo[b]furan-5-yl)-2｢,6｢-dihydroxy-4｢-methylpropiophenone 2｢-O-(6-O-methoxycarbonyl)-b-D-glucopyranoside), an orally active inhibitor of Na⁺-glucose cotransporter, on hyperglycemia and insulin resistance in skeletal muscle of streptozotocin (STZ)-induced diabetic rats. Chronic (4ﾊweeks) administration of T-1095 as food admixture (0.01-0.1% wt/wt) suppressed the blood glucose level without affecting the food intake and body weight. In addition, the reduced 2-deoxyglucose uptake and lactate release in the soleus muscle of STZ rat was ameliorated by chronic treatment of T-1095. These data suggest that T-1095 improves insulin sensitivity in skeletal muscle through correction of hyperglycemia and has novel therapeutic potential for treatment of diabetes mellitus through removing glucose toxicity.

Keywords: Diabetes-mellitus, Streptozotocin, Na⁺-glucose cotransporter