Serum free IGF-I during a hyperinsulinemic clamp following 3 days of administration of IGF-I vs. saline

In a random-ized crossover study in eight healthy subjects, we compared the effect of 3 days of continuous subcutaneous administration of insulin-like growth factor I (IGF-I; 10 /g'kg''-h"1) and saline on fasting serum levels of free IGF-I, total (extractable) IGF-I, and IGF-binding protein (IGFBP)-l and -3. On the 3rd day a hyperinsulinemic (euglycemic and hypoglycé mie) clamp was performed. When preclamp (baseline) levels were compared after 3 days, IGF-I administration had increased total IGF-I from 225 ± 21 (means ± SE) to 1, 003 ± 46 μg/ J (P < 0.0001), free IGF-I from 0.5 ± 0.2 to 10.4 ± 1.7 μg/l (P < 0.001), IGFBP-3 from 2, 908 ± 148 to 3, 591 ± 179 μg/l (P < 0.01), and IGFBP-1 from 7.6 ± 3.8 to 19.6 ± 2.5 fig/l (P < 0.01). During the clamp, levels of free IGF-I increased gradually from baseline to 1.0 ± 0.3 μg/l (saline; P < 0.01) and to 19.6 ± 4.7 μg/l (IGF-I; P < 0.005). Concomitantly, levels of IGFBP-1 decreased gradually from baseline to 4.1 ± 2.3 μg/l (saline; P < 0.0005) and to 4.6 ± 1.8 μg/ J (IGF-I; P < 0.0001). Total IGF-I exhibited minor changes only during the clamp (P < 0.05), and IGFBP-3 was unchanged. In conclusion, administration of IGF-I increased total IGF-I about fourfold, whereas free IGF-I increased 20-fold. Noteworthily, in both situations a further twofold increase in free IGF-I was observed during the hyperinsulinemic clamp, concomitant with a decrease in IGFBP-1. This supports the hypothesis that IGFBP-1 is important in the short-term regulation of free IGF-I in vivo.