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

Abstract

In a randomized 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 micrograms.kg-1.h-1) and saline on fasting serum levels of free IGF-I, total (extractable) IGF-I, and IGF-binding protein (IGFBP)-1 and -3. On the 3rd day a hyperinsulinemic (euglycemic and hypoglycemic) 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 micrograms/l (P < 0.0001), free IGF-I from 0.5 +/- 0.2 to 10.4 +/- 1.7 micrograms/l (P < 0.001), IGFBP-3 from 2,908 +/- 148 to 3,591 +/- 179 micrograms/l (P < 0.01), and IGFBP-1 from 7.6 +/- 3.8 to 19.6 +/- 2.5 micrograms/l (P < 0.01). During the clamp, levels of free IGF-I increased gradually from baseline to 1.0 +/- 0.3 micrograms/l (saline; P < 0.01) and to 19.6 +/- 4.7 micrograms/l (IGF-I; P < 0.005). Concomitantly, levels of IGFBP-1 decreased gradually from baseline to 4.1 +/- 2.3 micrograms/l (saline; P < 0.0005) and to 4.6 +/- 1.8 micrograms/l (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.