Insulin-Dependent Regulation of Insulin-Like Growth Factor-Binding Protein-1*

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Abstract
In previous studies it has been determined that food ingestion or glucose infusion suppresses serum insulin-like growth factor-binding protein-1 (IGFBP-1) concentrations in normal subjects. It has not been determined, however, whether glucose-dependent suppression is due to enhancement of insulin-stimulated glucose transport, to some other insulin-mediated effect, or to a direct effect of glucose. These studies were undertaken to determine if infusion of other nutrients or energy sources that activate glycolysis, but not insulin secretion, could lead to suppression of the plasma concentrations of this protein. After infusion of 50 g glucose over 4 h, the mean plasma IGFBP - 1 concentration fell from 44.2 .+-. 13.8 to 17.4 .+-. 8.1 .mu.g/L (P < 0.001). In contrast, when 50 g fructose were infused over 4 h, IGFBP-1 decreased from 44.6 .+-. 7.4 to only 32.7 .+-. 6.7 .mu.g/L (P < 0.01). Comparison of these changes showed that the mean decrease after glucose infusion was significantly greater than that after fructose (P < 0.01). In contrast to these decreases, infusion of an isocaloric amount of triglycerides resulted in no significant change in IGFBP-1 concentrations (from 49.8 .+-. 14.1 to 40.2 + 10.4 .mu.g/L; P = NS). Concomitant measurements of immunoreactive C-peptide during the glucose and fructose infusions showed that plasma C-peptide levels rose from 1.6 .+-. 0.2 to 3.9 .+-. 0.7 nM (P < 0.001) during the glucose infusion, whereas the maximum increase was from 1.7 .+-. 0.4 to only 2.3 .+-. 0.4 nM (P < 0.05) during the fructose infusion. The difference between these mean changes was also significant. The change in C-peptide correlated inversely with the changes in IGFBP-1 during the glucose infusion (r = -0.68; P < 0.001), but not during fructose infusion (r = -0.31). The results of this study suggest that insulin stimulation of cellular metabolic pathways is an important variable regulating the suppression of plasma IGFBP- 1 concentrations. Activation of noninsulin-dependent glycolytic pathways appears to result in an equivalent degree of suppression, whereas provision of other energy substrates has no effect. We conclude that both insulin and glucose are important regulators of plasma concentrations of IGFBP-1 in vivo, and in this way they may significantly influence IGF action.