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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

2002; Wiley; Volume: 29; Issue: 5-6 Linguagem: Inglês

10.1046/j.1440-1681.2002.03671.x

1440-1681

Kumiko Nunoi, Koichiro Yasuda, Tetsuya Adachi, Yoshimasa Okamoto, Nobuyuki Shihara, Mika Uno, Akiko Tamon, Naoko Suzuki, Akira Oku, Kinsuke Tsuda,

Pharmacology and Obesity Treatment

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 (HbA 1c ) 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 HbA 1c 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.