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The emerging role of NO and IGF‐1 in early renal hypertrophy in STZ‐induced diabetic rats
Author(s) -
LevinIaiomy,
Iaina Adrian,
Raz Itamar
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1172
Subject(s) - medicine , endocrinology , glomerular hyperfiltration , renal hypertrophy , diabetic nephropathy , streptozotocin , diabetes mellitus , igfbp3 , muscle hypertrophy , renal function , kidney , nephropathy , growth factor , receptor
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. Copyright © 2011 John Wiley & Sons, Ltd.