Antidiabetic effect of chronic administration of JTT-608, a new hypoglycemic agent, in diabetic Goto-Kakizaki rats.
We investigated the chronic effect of a new antidiabetic agent, trans-4-(methylcyclohexyl)-4-oxobutyric acid (JTT-608), in Goto-Kakizaki rats, a genetic model of non-obese type II diabetes mellitus. The rats were fed a liquid meal, three times a day, for 12 weeks. The rats were treated orally with JTT-608 (10-100 mg/kg) 10 min before each meal. Fasting blood glucose, triglyceride and hemoglobin A1c levels were reduced by JTT-608 at all dose levels during the experimental period. Blood glucagon-like peptide-1 level with 100 mg/kg JTT-608 increased at the end of the treatment period. JTT-608 (30-100 mg/kg) reduced urinary protein levels after administration for 5-12 weeks. In Goto-Kakizaki rats showing slight diabetic renal lesions, pathological examination revealed that JTT-608 reduced the incidence of vacuolation in renal tubules. JTT-608 (30-100 mg/kg) ameliorated the reduced motor nerve conduction velocities observed in the Goto-Kakizaki rats after administration for 12 weeks. We conclude that chronic administration of JTT-608 produces good blood glucose control and gradually arrests the development of diabetic neuropathy and nephropathy.
Ohta
Takeshi
T
Japan Tobacco, Inc., Central Pharmaceutical Research Institute, 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
Miyajima
Katsuhiro
K
Komuro
Goro
G
Furukawa
Noboru
N
Yonemori
Fumihiko
F
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology*; D003510:Cyclohexanes / Q000008:administration & dosage / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009431:Neural Conduction / Q000187:drug effects; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002087:Butyrates; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D014280:Triglycerides; C116719:4-(4-methylcyclohexyl)-4-oxobutyric acid