Aminoguanidine decreases urinary albumin and high-molecular-weight proteins in diabetic rats.
The effect of aminoguanidine (AG) on diabetic proteinuria was studied in control rats ([C]), streptozotocin (SZ)-induced diabetic rats ([DM]), control rats treated with AG [( C + AG]), or diabetic rats treated with AG [( DM + AG]). Increased glycation of hemoglobin (HbA1C), and glomerular basement membrane (GBM) type IV collagen (IV-C) at 10 wk of stable diabetes were associated with the appearance of high-molecular-weight (HMW) cross-linked type I collagen and HMW proteinuria of 62 kD, 69 kD albumin and 77 kD proteins to the levels of 362, 381, and 408%, while 9.9, 13.5, 17, 18, and 23 kD proteins were decreased, respectively, to non-detectable, 37, 16, and 13%. AG decreased cross-linkage of type I collagen and significantly decreased urinary 62 kD protein to 54%, 69 kD albumin to 40%, and 77 kD protein to 49% at 10 wk in [DM + AG] compared to [DM] without changing diabetic control. It is suggested that glycation-derived late-stage protein modification is etiologically important for diabetic proteinuria, and that AG can potentially prevent diabetic HMW proteinuria.
Itakura
M
M
Division of Endocrinology and Metabolism, University of Tsukuba, Ibaraki, Japan.
Yoshikawa
H
H
Bannai
C
C
Kato
M
M
Kunika
K
K
Kawakami
Y
Y
Yamaoka
T
T
Yamashita
K
K
D000419:Albuminuria / Q000188:drug therapy; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006146:Guanidines / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D003094:Collagen; D006442:Glycated Hemoglobin; D006146:Guanidines; C004479:pimagedine