Protein kinase C beta inhibitor prevents diabetic peripheral neuropathy, but not histopathological abnormalities of retina in Spontaneously Diabetic Torii rat.
Spontaneously Diabetic Torii (SDT) rat shows severe ocular complications such as tractional retinal detachment. In the present study, effect of protein kinase C beta (PKCbeta) inhibitor JTT-010 was evaluated to clarify the involvement of PKCbeta in complications of SDT rat. SDT rats were administered JTT-010 (10 or 50 mg/kg/day) for 48 weeks. SDT rats showed delayed oscillatory potentials in electroretinogram. Delayed motor nerve conduction velocity, decreased coefficients of variation of R-R intervals in electrocardiogram and thermal hypoalgesia were also observed. These functional disorders were prevented by administration of JTT-010. Abnormal retinal vascular was formed and the optic disc was protruded in SDT rat; however, JTT-010 did not prevent these hyperglycaemia-induced retinal abnormalities. These findings indicate that PKCbeta is intimately involved in diabetic complications; however, it seems that other factor(s) are primary contributors to histopathological abnormalities in retina. Therefore, PKCbeta inhibitors require concurrent administration of antihyperglycaemic drugs to achieve maximum effect on diabetic complications.
Sasase
T
T
Japan Tobacco, Central Pharmaceutical Research Institute, Biological/Pharmacological Research Laboratories, 1-1 Murasaki-cho, Takatsuki,Osaka, Japan. tomohiko.sasase@jt.com
Morinaga
H
H
Abe
T
T
Miyajima
K
K
Ohta
T
T
Shinohara
M
M
Matsushita
M
M
Kakehashi
A
A
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D004195:Disease Models, Animal; D007189:Indans / Q000494:pharmacology*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D064546:Protein Kinase C beta; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats
C508122:(2R)-3-(2-aminomethyl-2,3-dihydro-1H-3a-azacyclopenta(a)inden-8-yl)-4-phenylaminopyrrole-2,5-dione monomethanesulphonate; D007189:Indans; D011758:Pyrroles; D011493:Protein Kinase C; D064546:Protein Kinase C beta