Beneficial effect of T-1095, a selective inhibitor of renal Na+-glucose cotransporters, on metabolic index and insulin secretion in spontaneously diabetic GK rats.
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.
Nunoi
Kumiko
K
Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.
Yasuda
Koichiro
K
Adachi
Tetsuya
T
Okamoto
Yoshimasa
Y
Shihara
Nobuyuki
N
Uno
Mika
M
Tamon
Akiko
A
Suzuki
Naoko
N
Oku
Akira
A
Tsuda
Kinsuke
K
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002254:Carbonates / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000032:analysis; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010179:Pancreas / Q000503:physiopathology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
D001786:Blood Glucose; D002254:Carbonates; D005947:Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012964:Sodium; C121396:T 1095