Biomaterial Database

Inhibition of renal ornithine decarboxylase activity prevents kidney hypertrophy in experimental diabetes. 1993

S B Pedersen, and A Flyvbjerg, and B Richelsen

Division of Endocrinology and Metabolism, University Clinic of Internal Medicine, Aarhus Amtssygehus, Denmark.

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.

UI	MeSH Term	Description	Entries
D006984	Hypertrophy	General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA).	Hypertrophies
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008297	Male		Males
D009929	Organ Size	The measurement of an organ in volume, mass, or heaviness.	Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D009955	Ornithine Decarboxylase	A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated S-adenosylmethionine to form spermidine.	Ornithine Carboxy-lyase,Carboxy-lyase, Ornithine,Decarboxylase, Ornithine,Ornithine Carboxy lyase
D003921	Diabetes Mellitus, Experimental	Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.	Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D000518	Eflornithine	An inhibitor of ORNITHINE DECARBOXYLASE, the rate limiting enzyme of the polyamine biosynthetic pathway.	Difluoromethylornithine,alpha-Difluoromethylornithine,DL-alpha-Difluoromethylornithine,Eflornithine Hydrochloride,Eflornithine Monohydrochloride, Monohydrate,MDL-71,782 A,Ornidyl,RMI 71782,Vaniqa,alpha-Difluoromethyl Ornithine,DL alpha Difluoromethylornithine,MDL 71,782 A,MDL71,782 A,Ornithine, alpha-Difluoromethyl,alpha Difluoromethyl Ornithine,alpha Difluoromethylornithine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D017208	Rats, Wistar	A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.	Wistar Rat,Rat, Wistar,Wistar Rats