THE EFFECT OF SUBSTANCE-L ON GLUCOSE-MEDIATED CROSS-LINKS OF COLLAGEN IN THE DIABETIC DB/DB MOUSE

被引:13
作者
LUBEC, G [1 ]
BARTOSCH, B [1 ]
MALLINGER, R [1 ]
ADAMIKER, D [1 ]
GRAEF, I [1 ]
FRISCH, H [1 ]
HOGER, H [1 ]
机构
[1] UNIV VIENNA, DEPT PEDIAT, A-1010 VIENNA, AUSTRIA
关键词
collagen; cross-links; db/db mice; diabetes; glomerular basement membrane; long-term complications; nephropathy; renal changes; substance L;
D O I
10.1159/000186155
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Genetically diabetic mice (db/db) were given 50 mg/kg body weight/day substance L, a nontoxic basic amino acid and compared to control diabetic mice without treatment. The oral administration of the compound was started at the age of 3 months and the animals were sacrificed at the age of 7 months. No adverse effects were observed in animals given the substance L. Total food consumption, drinking water intake and body weight were comparable between the groups. Nonenzymatic glycosylation of serum proteins and hemoglobin was not significantly different in the groups. Renal pathological lesions in the control diabetic mice showed glomerular mesangial expansion and on electron microscopy thickened glomerular basement membranes with a mean thickness of 3,204 ± 186 Å. Treated animals showed significantly less mesangial crescents and thinner glomerular basement membrane thickness of 2,520 ± 252 Å (p < 0.01). The experimental animals showed in addition a lower mean kidney weight. Glomerular but not tubular proteinuria was reduced in the treated group. Basement membrane collagen type IV isolated from kidneys of experimental animals was more soluble in acidity and showed a lower degree of cross-linking as evaluated by SDS-polyacrylamide gel electrophoresis. We conclude that substance L is beneficial to diabetic renal changes. We suggest that this positive effect could be due to the inhibition of glucose-mediated abnormal cross-linking of collagenous structures by the interaction of substance L with reactive carbonyl residues of glycosylation adducts of collagen. Other possible mechanisms are discussed .
引用
收藏
页码:281 / 284
页数:4
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