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Beneficial Effect Of T-1095, A Selective Inhibitor Of Renal Na+–Glucose Cotransporters, On Metabolic Index And Insulin Secretion In Spontaneously Diabetic Gk Rats

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SUMMARY

1. To investigate the pharmacological effects of T-1095, this novel derivative of phlorizin was administered to GK rats for 8 weeks. T-1095 treatment significantly lowered plasma glucose and glycosylated haemoglobin (HbA1c) levels, but did not significantly affect bodyweight.

2. T-1095 treatment did not affect 3.3 mmol/L glucose-induced insulin secretion in the isolated perfused pancreas of GK rats.

3. The peak insulin release in T-1095-treated GK rats was significantly higher during the first phase than in untreated GK rats (3–4 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the first phase in T-1095-treated GK rats was significantly higher than in untreated GK rats (35.3 ± 1.4 vs 27.3 ± 2.5 ng in T-1095-treated compared with untreated rats, respectively).

4. During the second phase, insulin release in T-1095-treated GK rats was somewhat higher than in untreated GK rats (7–30 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the second phase in T-1095-treated GK rats was significantly higher than in untreated GK rats (88.2 ± 6.1 vs 68.1 ± 5.7 ng, respectively).

5. The total amount of insulin secreted during perfusion in T-1095-treated GK rats was significantly higher than in untreated GK rats (123.5 ± 7.3 vs 95.4 ± 7.7 ng, respectively).

6. These data show that the metabolic indices, plasma glucose and HbA1c levels and insulin secretion are significantly improved by T-1095 treatment in GK rats, which are spontaneously diabetic rats, suggesting its usefulness as a novel oral therapeutic antidiabetic agent.
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Keywords: insulin secretion; perfused pancreas; phlorizin; type 2 diabetes

Document Type: Research Article

Affiliations: 1: Laboratory of Metabolism, Graduate School of Human and Environmental Studies, 2: Laboratory of Metabolism, Faculty of Integrated Human Studies, 3: Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan and 4: Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd, Saitama, Japan

Publication date: May 1, 2002

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