Inhibition of renal ornithine decarboxylase activity fails to reduce kidney size and urinary albumin excretion in diabetic rats with manifest kidney hypertrophy.
Formation of polyamines has previously been shown to play an important role for initial kidney growth in experimental diabetes, as treatment of diabetic rats with a selective ornithine decarboxylase (ODC) inhibitor, initiated immediately after diabetes induction, abolishes the initial kidney growth. In order to investigate the role of polyamine formation for the maintenance of diabetic kidney hypertrophy, ODC inhibition was initiated after manifest kidney hypertrophy had occurred. The kidney weight in diabetic rats was significantly larger than in control rats after a diabetes duration of 7, 14, 50 and 71 days and the total glomerular volume was increased in kidneys from diabetic rats after a diabetes duration of 71 days. Renal activity of ODC was increased in diabetic rats throughout the study period of 71 days. Treatment of diabetic rats with the selective ODC inhibitor di-fluoro-methyl-ornithine (DFMO) was maintained for two periods (days 7-14 and days 50-71). DFMO treatment had no effect on 24-h food consumption, blood glucose concentration or body weight. However, despite almost total inhibition of the kidney ODC activity, there was no effect on kidney growth or total glomerular volume in the DFMO treated diabetic rats compared to placebo treated diabetic rats. Finally, the urinary albumin excretion was markedly increased in diabetic rats with no effects of ODC-inhibition. In conclusion, inhibition of ODC initiated in diabetic rats with manifest kidney enlargement had no effect on renal size, glomerular volume or urinary albumin excretion. These findings together with our previous findings indicate that the role of polyamines in diabetic kidney enlargement is restricted to the first week after diabetes induction.
Pedersen
S B
SB
University Clinic of Internal Medicine, Division of Endocrinology and Metabolism, Aarhus Amtssygehus, Denmark.
Bjørn
S F
SF
Richelsen
B
B
Flyvbjerg
A
A
D000419:Albuminuria / Q000209:etiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004231:Diuresis / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006984:Hypertrophy; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000502:physiology; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D001786:Blood Glucose; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D013311:Streptozocin; D009955:Ornithine Decarboxylase; D000518:Eflornithine