The emerging role of NO and IGF-1 in early renal hypertrophy in STZ-induced diabetic rats

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 NO2 + NO3 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 (c) 2011 John Wiley & Sons, Ltd.