A new prostaglandin E1 analogue (TFC-612) improves the reduction in motor nerve conduction velocity in spontaneously diabetic GK (Goto-Kakizaki) rats.
A new prostaglandin E1 analogue, TFC-612, was given orally to 2 month-old spontaneously diabetic GK (Goto-Kakizaki) rats for 3 months to ascertain its effects on reduced motor nerve conduction velocity (MCV). A high dose of this compound (0.3 mg/kg body weight) significantly restored MCV after 2 and 3 months of administration, although the low dose (0.03 mg/kg body weight) did not. In addition, 1 month administration of TFC-612 significantly improved the reduced MCV in aged (5 month-old) GK rats only in the high dose group (0.3 mg/kg body weight), but not in the low dose group (0.03 mg/kg body weight). Although TFC-612 significantly suppressed sorbitol accumulation in the sciatic nerves of GK rats in a dose dependent manner after 3 months administration, this suppression was not observed after either 2 months administration to 2 month-old GK rats or after 1 month administration to 5 month-old GK rats. Fasting blood glucose levels of all GK rats remained high throughout the experiments, regardless of TFC-612 administration. TFC-612's improvement on reduced motor nerve conduction velocity was related partly to suppression of sorbitol accumulation, but other factors, including microcirculation, may contribute significantly to this effect. These results suggest that TFC-612 may be beneficial in the treatment of diabetic nerve impairment.
Suzuki
K
K
Third Department of Internal Medicine, Tohoku University School of Medicine, Miyagi, Japan.
Saito
N
N
Sakata
Y
Y
Toyota
T
T
Goto
Y
Y
D000375:Aging; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013012:Sorbitol / Q000378:metabolism
D001786:Blood Glucose; D013012:Sorbitol; C054546:TFC 612; D000527:Alprostadil