T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes

被引:226
作者
Oku, A
Ueta, K
Arakawa, K
Ishihara, T
Nawano, M
Kuronuma, Y
Matsumoto, M
Saito, A
Tsujihara, K
Anai, M
Asano, T
Kanai, Y
Endou, H
机构
[1] Tanabe Seiyaku Co Ltd, Analyt Res Lab, Osaka, Japan
[2] Univ Tokyo, Fac Med, Dept Internal Med 3, Tokyo, Japan
[3] Kyorin Univ, Sch Med, Fac Med, Dept Pharmacol & Toxicol, Tokyo, Japan
关键词
D O I
10.2337/diabetes.48.9.1794
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
T-1095A and T-1095 are synthetic agents derived from phlorizin, a specific inhibitor of Na+-glucose cotransporters (SGLTs). Unlike phlorizin, T-1095 is absorbed into the circulation via oral administration, is metabolized to the active form, T-1095A, and suppresses the activity of SGLTs in the kidney. Orally administered T-1095 increases urinary glucose excretion in diabetic animals, thereby decreasing blood glucose levels. Indeed, the postprandial hyperglycemia after a meal load was shown to be suppressed by this compound in streptozotocin (STZ)-induced diabetic rats. With longterm T-1095 treatment, both blood glucose and HbA(1c) levels were reduced in STZ-induced diabetic rats and yellow KK mice. In addition, there was amelioration of abnormal carbohydrate metabolism, i.e., hyperinsulinemia and hypertriglyceridemia, and of the development of microalbuminuria, in yellow KK mice. Thus T-1095 may be a useful antidiabetic drug, providing a novel therapeutic approach for diabetes.
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页码:1794 / 1800
页数:7
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