Correction of Hyperglycemia and Insulin Sensitivity by T-1095, an Inhibitor of Renal Na+-Glucose Cotransporters, in Streptozotocin-Induced Diabetic Rats
Open Access
- 1 January 2000
- journal article
- Published by Elsevier in The Japanese Journal of Pharmacology
- Vol. 84 (3), 351-354
- https://doi.org/10.1254/jjp.84.351
Abstract
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.Keywords
This publication has 13 references indexed in Scilit:
- Hyperglycemia contributes insulin resistance in hepatic and adipose tissue but not skeletal muscle of ZDF ratsAmerican Journal of Physiology-Endocrinology and Metabolism, 2000
- Hyperglycemia Impairs the Insulin Signaling Step between PI 3-Kinase and Akt/PKB Activations in ZDF Rat LiverBiochemical and Biophysical Research Communications, 1999
- Na+-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4‘-Dehydroxyphlorizin Derivatives Substituted on the B RingJournal of Medicinal Chemistry, 1999
- T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes.Diabetes, 1999
- Glucose Transport: Pivotal Step in Insulin ActionDiabetes, 1996
- DIABETES CONTROL AND COMPLICATIONSAnnual Review of Medicine, 1995
- The contribution of hyperglycaemia and hypoinsulinaemia to the insulin resistance of streptozotocin-diabetic ratsDiabetologia, 1992
- Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: Evidence for reversal following phlorizin treatmentMetabolism, 1990
- Glucose ToxicityDiabetes Care, 1990
- Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats.JCI Insight, 1987