title: Protein kinase C beta inhibitor prevents diabetic peripheral neuropathy, but not histopathological abnormalities of retina in Spontaneously Diabetic Torii rat.
abstract: 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.
authors.affiliation: Japan Tobacco, Central Pharmaceutical Research Institute, Biological/Pharmacological Research Laboratories, 1-1 Murasaki-cho, Takatsuki,Osaka, Japan. tomohiko.sasase@jt.com
authors.forename: T
authors.initials: T
authors.lastname: Sasase
authors.forename: H
authors.initials: H
authors.lastname: Morinaga
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: K
authors.initials: K
authors.lastname: Miyajima
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Shinohara
authors.forename: M
authors.initials: M
authors.lastname: Matsushita
authors.forename: A
authors.initials: A
authors.lastname: Kakehashi
mesh_terms: 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
chemical_list: 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