title: The emerging role of NO and IGF-1 in early renal hypertrophy in STZ-induced diabetic rats.
abstract: BACKGROUND
  Diabetic nephropathy (DN) is a major complication of diabetes mellitus, and the most common cause of end-stage renal disease. DN is characterized by early hyperfiltration and renal hypertrophy, which are associated with increased renal insulin-like growth factor-1 (IGF-1) levels. The relationship between IGF-1 and nitric oxide (NO) in DN is not established. The aim of this study was to investigate the effects of NO system modulation on the IGF-1-mediated hypertrophy and hyperfiltration during the first week after diabetes induction.
  
  
  METHODS
  Diabetes was induced in rats by streptozotocin (STZ) injection. Diabetic rats were treated with NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME). Various serum IGF-binding proteins (IGFBPs) and renal IGFBP1 expression was evaluated. Urine and plasma NO(2) + NO(3) level analysis was also performed.
  
  
  RESULTS
  STZ induced hyperglycaemia decreased plasma insulin levels and brought about a decrease in body weight. L-NAME administration to diabetic rats significantly prevented renal hypertrophy and hyperfiltration. Serum IGFBP3, IGFBP4 and 30-kDa IGFBP fraction were all significantly reduced in diabetic rats, compared with those in non-diabetic control rats. However, the renal IGFBP1 mRNA expression in diabetic rats was significantly higher. These changes were accompanied by an increased in NO production. L-NAME administration prevented the serum IGFBP decline, without significantly affecting the renal IGFBP1 mRNA expression.
  
  
  CONCLUSIONS
  We have shown that increased renal IGF-1 and increased NO production during the very early stages of STZ-induced DN are associated with renal hypertrophy and hyperfiltration in diabetic rats. Modulating the IGF-1 availability to the kidney by nitric oxide synthase inhibition significantly reduced renal hypertrophy and hyperfiltration during the first week of STZ-induced diabetes mellitus.
authors.affiliation: Department of Nephrology and Hypertension, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Hashomer, Israel. lironomy@gmail.com.
authors.forename: Nomy
authors.initials: N
authors.lastname: Levin-Iaina
authors.forename: Adrian
authors.initials: A
authors.lastname: Iaina
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D005260:Female; D006984:Hypertrophy; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007668:Kidney / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009589:Nitrogen Oxides / Q000378:metabolism; D051381:Rats
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D009589:Nitrogen Oxides; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester