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: Nomy Levin-Iaina, Adrian Iaina, Itamar Raz
• Journal: Diabetes/metabolism research and reviews (Diabetes Metab Res Rev) Vol. 27 Issue 3 Pg. 235-43 (Mar 2011) ISSN: 1520-7560 [Electronic] England
• PMID: 21309053 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• Insulin-Like Growth Factor Binding Protein 1
• Insulin-Like Growth Factor Binding Proteins
• Nitrogen Oxides
• Nitric Oxide
• Insulin-Like Growth Factor I
• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Diabetes Mellitus, Experimental (metabolism)
• Diabetic Nephropathies (prevention & control)
• Female
• Hypertrophy
• Insulin-Like Growth Factor Binding Protein 1 (metabolism)
• Insulin-Like Growth Factor Binding Proteins (metabolism)
• Insulin-Like Growth Factor I (physiology)
• Kidney (pathology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (physiology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitrogen Oxides (metabolism)
• Rats