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

Abstract

We investigated the effects of T-1095 (3-(benzo[b]furan-5-yl)-2′, 6′-dihydroxy-4′-methylpropiophenone 2′-O-(6-O-methoxycarbonyl)-β-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 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.