A SINGLE DOSE OF RECOMBINANT HUMAN IGF-I (rhIGF-I) DOES NOT AFFECT URINARY EXCRETION OF NITRIC OXIDE METABOLITES IN IDDM. 560

Abstract

Several studies have shown the potential importance of nitric oxide (NO) in the regulation of peripheral vascular resistance in diabetes. The discovery that IGF-I induces NO production by endothelial cells suggests that IGF-I may be an important regulator of vascular tone in vivo via nitric oxide release from the vascular endothelium and may play a role in control of renal hemodynamics in physiologic and pathologic conditions. We have previously reported that the excretion of NO metabolites(NO2+NO3=NOx) is not significantly different in IDDM compared to controls (n=9; age range 3-17 years). The aim of this study was to evaluate urinary excretion of NOx in response to a single rhIGF-I (n=9; 80 mcg/Kg Sc) or placebo injection (n=9). Urinary excretion of NOx was measured during hospital admission in the 12-hour period preceding and following rhIGF-I or placebo administration in 18 subjects with IDDM without nephropathy (age range 8-16 years, IDDM duration 1-10.5 years, 5 pre-pubertal/13 pubertal). Mean glycosylated hemoglobin was high(11.7±1.9%; nI 4.4-6.1%) while on conventional insulin therapy. Urinary NO3 was reduced to NO2 by E. Coli reductase and total NO2 was analyzed using the Griess reagent. Records were kept by the nurses and accuracy of the collection was validated by creatinine excretion (correlation between creatinine and urinary NO, r=0.51; p<0.01). The data(mean±SD) were analyzed by Student's t-test. A single injection of rhIGF-I did not affect the urinary excretion of NO metabolites. As previously reported, the mean nitric oxide excretion was not significantly different from that observed in controls and did not increase with IDDM duration. Further studies are necessary to evaluate the influence of chronic rhIGF-I administration on nitric oxide metabolism. This study was partially funded by Genentech Inc. and NY State Health Research Council.Table