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The Effect of Oral Glucose on Serum Free Insulin-Like Growth Factor-I and -II in Healthy Adults¹

Institute of Experimental Clinical Research, Medical Research Laboratories, Aarhus University Hospital, Denmark

Address correspondence and requests for reprints to: Jan Frystyk, MD, PhD, Institute of Experimental Clinical Research, Aarhus Kommune Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark.

Insulin-like growth factor (IGF) binding protein-I (IGFBP-1) has been suggested to regulate the availability of free IGF and the glucose lowering activity of the IGF-system in relation to fuel supply. Our recent observations of significant inverse correlations between free IGF-I and IGFBP-1 in cross-sectionally collected fasting serum samples support a possible physiological association between the peptides. To further study the impact of IGFBP-1 on free IGF levels and the possible participation of the IGF-system in glucose homeostasis, we studied the time course of changes in IGFBP-1 and free IGFs in 13 healthy subjects undergoing an oral glucose tolerance test (OGTT). Serum was collected every 30 min for 330 min.

Glucose, insulin, and GH followed the expected patterns and had regained baseline levels at 270 min. Total IGF-I and free and total IGF-II remained unaltered. IGFBP-1 decreased significantly by 37–52% (P < 0.05) from 150 to 210 min, whereafter the concentration gradually increased by 75% to a level that tended to be above baseline (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 free 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 to IGFBP-1. Insulin, but not free IGF-I, correlated significantly with serum glucose (P < 0.05).

These results extend our previous findings of an inverse correlation between free IGF-I and IGFBP-1 in cross-sectional studies to include longitudinal observations, and thus further substantiates the hypothesis that IGFBP-1 is an important determinant of free IGF-I in vivo. Significant changes in free IGF-I were observed only in the late postprandial phase, when glucose and insulin were fully normalized, demonstrating that free IGFs probably do not participate in glucoregulation to any significant degree during an oral glucose load in healthy subjects.

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