INSULIN-LIKE GROWTH-FACTORS (IGF) I AND II AND IGF BINDING-PROTEINS 1, 2 AND 3 DURING LOW-DOSE GROWTH-HORMONE (GH) INFUSION AND SEQUENTIAL EUGLYCEMIC AND HYPOGLYCEMIC GLUCOSE CLAMPS - STUDIES IN GH-DEFICIENT PATIENTS

To evaluate the short-term effects of growth hormone (GH), insulin and different levels of glycemia on insulin-like growth factors (IGF) I and II and IGF binding proteins (IGFBP) 1, 2 and 3. we studied six GH-deficient adolescents during a night and the following day in the postabsorptive (basal) state followed by sequential euglycemic (5 mmol/l) and hypoglycemic (3 mmol/l) glucose clamps concomitant with an intravenous infusion (starting at 24.00 h) of GH (35 mug/h) or saline. Current GH therapy was withdrawn 24 h prior to each study. Nocturnal levels of IGF-I, IGF-II, IGFBP-2 and IGFBP- 3 remained stable during both studies. Nocturnal serum IGFBP-1 increased and correlated inversely with insulin in both studies. Regression analysis revealed a significant inverse correlation between mean nocturnal IGFBP-2 and IGFBP-3 levels. During the daytime, serum IGF-I declined slowly during saline infusion, whereas serum IGF-II remained stable in both studies. Serum IGFBP-1 displayed a gradual significant decline during the basal state and the euglycemic and hypoglycemic clamps seemed to be unaffected by GH levels. By contrast, serum IGFBP-2 remained stable during the same period in both the GH and the saline study. Serum IGFBP-3 declined insignificantly during the daytime in the saline study. In conclusion: a strong inverse correlation between IGFBP-1 and insulin is confirmed: serum IGFBP-2 exhibits a constant circadian pattern, which seems independent of both ambient glucose and insulin levels and short-term GH deprivation but, on the other hand. shows a strong inverse correlation with IGFBP-3 levels: it is possible that IGFBP-2 levels are regulated by IGFBP-3 or IGFBP-3 binding site availability.