Inhibition of renal ornithine decarboxylase activity prevents kidney hypertrophy in experimental diabetes.
The selective ornithine decarboxylase (ODC) inhibitor difluoromethyl ornithine (DFMO) was used to investigate the role of polyamines in initial diabetic renal enlargement. ODC activity in kidneys from diabetic animals was increased (fivefold) 24 h after diabetes induction (P < 0.05), and throughout the study (7 days) the activity remained 2- to 3-fold elevated (P < 0.05). Insulin treatment normalized renal ODC activity, whereas DFMO treatment totally inhibited the kidney ODC activity. The kidney weight in diabetic rats was 21% higher than that of control rats (1,074 +/- 35 mg and 889 +/- 16 mg, P < 0.001). Insulin treatment normalized kidney weight (847 +/- 13 mg). Despite unaltered diabetic metabolic aberrations the kidney weight in DFMO-treated diabetic rats was normalized (911 +/- 7 mg). In conclusion, the ODC activity in diabetic kidneys undergoing hypertrophy was increased. Insulin treatment normalized both kidney weight and kidney ODC activity. Finally, selective inhibition of ODC activity by DFMO resulted in kidneys of normal size, despite unaltered diabetic metabolic aberrations. These findings support the hypothesis that polyamines play an important role in initial diabetic renal enlargement.
Pedersen
S B
SB
Division of Endocrinology and Metabolism, University Clinic of Internal Medicine, Aarhus Amtssygehus, Denmark.
Flyvbjerg
A
A
Richelsen
B
B
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology*; D000518:Eflornithine / Q000494:pharmacology*; D006984:Hypertrophy; D007328:Insulin / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009929:Organ Size; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D009955:Ornithine Decarboxylase; D000518:Eflornithine