THE EFFECT OF ORAL GLUCOSE ON SERUM-FREE INSULIN-LIKE GROWTH-FACTOR-IAND GROWTH-FACTOR-II IN HEALTHY-ADULTS

Insulin-like growth factor (IGF) binding protein-I (IGFBP-1) has been suggested to regulate the availability of free IGF and the glucose low ering activity of the IGF-system in relation to fuel supply. Our recen t observations of significant inverse correlations between free IGF-I and IGFBP-1 in cross-sectionally collected fasting serum samples suppo rt a possible physiological association between the peptides. To furth er study the impact of IGFBP-1 on free IGF levels and the possible par ticipation of the IGF-system in glucose homeostasis, we studied the ti me course of changes in IGFBP-1 and free IGFs in 13 healthy subjects u ndergoing an oral glucose tolerance test (OGTT). Serum was collected e very 30 min for 330 min. Glucose, insulin, and GH followed the expecte d patterns and had regained baseline levels at 270 min. Total IGF-I an d free and total IGF-II remained unaltered. IGFBP-1 decreased signific antly by 37-52% (P < 0.05) from 150 to 210 min, whereafter the concent ration gradually increased by 75% to a level that tended to be above b aseline (P = 0.052). Free IGF-I decreased by 29-38% (P < 0.05) at the end of the study (270-330 min). IGFBP-1 was inversely correlated to fr ee IGF-I at baseline (r = -0.57; P < 0.05), as well as during the OGTT (r = 0.66; P < 0.0001). In contrast, free IGF-II was not correlated t o IGFBP-1. Insulin, but not free IGF-I, correlated significantly with serum glucose (P < 0.05). These results extend our previous findings o f an inverse correlation between free IGF-I and IGFBP-1 in cross-secti onal studies to include longitudinal observations, and thus further su bstantiates the hypothesis that IGFBP-1 is an important determinant of free IGF-I in vivo. Significant changes in free IGF-I were observed o nly in the late postprandial phase, when glucose and insulin were full y normalized, demonstrating that free IGFs probably do not participate in glucoregulation to any significant degree during an oral glucose l oad in healthy subjects.