A protein kinase C-β-selective inhibitor ameliorates neural dysfunction in streptozotocin-induced diabetic rats

被引：182

作者：

Nakamura, J ^{[1
]}

Kato, K ^{[1
]}

Hamada, Y ^{[1
]}

Nakayama, M ^{[1
]}

Chaya, S ^{[1
]}

Nakashima, E ^{[1
]}

Naruse, K ^{[1
]}

Kasuya, Y ^{[1
]}

Mizubayashi, R ^{[1
]}

Miwa, K ^{[1
]}

Yasuda, Y ^{[1
]}

Kamiya, H ^{[1
]}

Ienaga, K ^{[1
]}

Sakakibara, F ^{[1
]}

Koh, N ^{[1
]}

Hotta, N ^{[1
]}

机构：

[1] Nagoya Univ, Sch Med, Dept Internal Med 3, Showa Ku, Nagoya, Aichi 4668550, Japan

来源：

DIABETES | 1999年 / 48卷 / 10期

关键词：

D O I：

10.2337/diabetes.48.10.2090

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Increased protein kinase C (PKC) activity has been implicated in the pathogenesis of diabetic retinopathy and nephropathy. However the role of PHC in diabetic neuropaths remains unclear The present study was conducted to compare the effect of PHC inhibition by a PKC-beta-selective inhibitor LY333531 (LY), on diabetic nerve dysfunction with that of an aldose reductase inhibitor, NZ-314 (NZ). Streptozotocin-induced diabetic rats were treated with or without LY and/or NZ for 4 weeks, and motor nerve conduction velocity (MNCV), coefficient of variation of R-R interval (C VR-R), sciatic nerve blood flow (SNBF), peak latencies of oscillatory potentials on electroretinogram, PKC activities in membranous and cytosolic fractions of sciatic nerves, and polyol contents in the tail nerves were measured. Untreated diabetic rats demonstrated delayed MNCV decreased CVR-R, reduced SNBF, and prolonged peak latencies of oscillatory potentials. Treatment with LP as well as NZ prevented all these deficits in diabetic rats. There were no significant differences in PKC activities in membranous or cytosolic fractions of sciatic nerves between normal and diabetic rats. Treatment with neither LY nor NZ altered PKC activities. Nerve myo-inositol depletion in diabetic rats was ameliorated not only by NZ, but also by LY These observations suggest that inhibition of PBC-beta by LY may hare a beneficial effect in preventing the development of diabetic nerve dysfunction, and that this effect may be mediated through its action on the endoneurial micro-vasculature.

引用

页码：2090 / 2095

页数：6

共 49 条

[1]

ALGVERE P, 1968, ACTA OPHTHALMOL, V46, P993

[2]

BORGHINI I, 1994, J NEUROCHEM, V62, P686

[3] Reversal of defective peripheral nerve conduction velocity, nutritive endoneurial blood flow, and oxygenation by a novel aldose reductase inhibitor, WAY-121,509, in streptozotocin-induced diabetic rats [J].

Cameron, NE ;

Cotter, MA ;

Dines, KC ;

Hohman, TC .

JOURNAL OF DIABETES AND ITS COMPLICATIONS, 1996, 10 (01) :43-53

[4] Metabolic and vascular factors in the pathogenesis of diabetic neuropathy [J].

Cameron, NE ;

Cotter, MA .

DIABETES, 1997, 46 :S31-S37

[5] THE RELATIONSHIP OF VASCULAR CHANGES TO METABOLIC FACTORS IN DIABETES-MELLITUS AND THEIR ROLE IN THE DEVELOPMENT OF PERIPHERAL-NERVE COMPLICATIONS [J].

CAMERON, NE ;

COTTER, MA .

DIABETES-METABOLISM REVIEWS, 1994, 10 (03) :189-224

[6]

COHEN RA, 1993, CIRCULATION, V87, P67

[7] NERVE FUNCTION IN GALACTOSAEMIC RATS - EFFECTS OF EVENING PRIMROSE OIL AND DOXAZOSIN [J].

DINES, KC ;

COTTER, MA ;

CAMERON, NE .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1995, 281 (03) :303-309

[8]

GREENE DA, 1989, CRIT REV NEUROBIOL, V5, P143

[9] COMPLICATIONS - NEUROPATHY, PATHOGENETIC CONSIDERATIONS [J].

GREENE, DA ;

SIMA, AAF ;

STEVENS, MJ ;

FELDMAN, EL ;

LATTIMER, SA .

DIABETES CARE, 1992, 15 (12) :1902-1925

[10] SUSTAINED RECOVERY OF NA+-K+-ATPASE ACTIVITY IN SCIATIC-NERVE OF DIABETIC MICE BY ADMINISTRATION OF H7 OR CALPHOSTIN-C, INHIBITORS OF PKC [J].

HERMENEGILDO, C ;

FELIPO, V ;

MINANA, MD ;

ROMERO, FJ ;

GRISOLIA, S .

DIABETES, 1993, 42 (02) :257-262

← 1 2 3 4 5 →