Correction of hyperglycemia and insulin sensitivity by T-1095, an inhibitor of renal Na+-glucose cotransporters, in streptozotocin-induced diabetic rats.
We investigated the effects of T-1095 (3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl)-beta-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.
Oku
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A
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
Ueta
K
K
Arakawa
K
K
Kano-Ishihara
T
T
Matsumoto
T
T
Adachi
T
T
Yasuda
K
K
Tsuda
K
K
Ikezawa
K
K
Saito
A
A
D000818:Animals; D002254:Carbonates / Q000627:therapeutic use*; D003847:Deoxyglucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005960:Glucosides / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007333:Insulin Resistance; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors*; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats
D002254:Carbonates; D005960:Glucosides; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; C121396:T 1095; D019344:Lactic Acid; D003847:Deoxyglucose